Total submissions: 15
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Daryl Scott Lab, |
RCV005862707 | SCV006555457 | pathogenic | L1CAM-related disorder | 2025-08-25 | criteria provided, single submitter | clinical testing | PS4, PM2, PP1, PP4 |
| Fulgent Genetics, |
RCV005049327 | SCV005683070 | likely pathogenic | MASA syndrome; X-linked complicated corpus callosum dysgenesis; X-linked hydrocephalus syndrome | 2024-05-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001093004 | SCV005626506 | likely pathogenic | not provided | 2024-07-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8929944, 31474318, 16650080, 25641508) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689412 | SCV005185927 | likely pathogenic | L1 syndrome | 2024-05-03 | criteria provided, single submitter | clinical testing | Variant summary: L1CAM c.719C>T (p.Pro240Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 182408 control chromosomes. c.719C>T has been reported in the literature in four individuals affected with L1 Syndrome (example, Aldinger_2019, Basel-Vanagaite_2006, Gu_1996). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31474318, 16650080, 8929944). ClinVar contains an entry for this variant (Variation ID: 10001). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Institute of Human Genetics, |
RCV004527287 | SCV005038684 | likely pathogenic | MASA syndrome | criteria provided, single submitter | not provided | ||
| Labcorp Genetics |
RCV003588562 | SCV004298799 | likely pathogenic | Spastic paraplegia | 2023-01-17 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 10001). This missense change has been observed in individuals with clinical features of L1 syndrome (PMID: 8929944, 10797421, 16650080, 31474318). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 240 of the L1CAM protein (p.Pro240Leu). |
| Eurofins- |
RCV000010684 | SCV003935109 | pathogenic | X-linked complicated corpus callosum dysgenesis | 2022-10-24 | criteria provided, single submitter | clinical testing | |
| Equipe Genetique des Anomalies du Developpement, |
RCV000010684 | SCV003843199 | pathogenic | X-linked complicated corpus callosum dysgenesis | 2019-09-04 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV000010684 | SCV002557412 | pathogenic | X-linked complicated corpus callosum dysgenesis | 2022-06-24 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with partial agenesis of corpus callosum (MIM#304100), MASA/CRASH syndrome (MIM#303350) and hydrocephalus due to aqueductal stenosis/with congenital idiopathic intestinal pseudoobstruction/with Hirschsprung disease (MIM#307000). (I) 0109 - This gene is associated with X-linked recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Both inter and intra-familial variability have been reported (PMID: 7562969, 16650080). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated Immunoglobulin domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been reported in at least five unrelated males with a variety of brain abnormalities namely syndromic hydrocephalus (PMID: 8929944), hypoplastic corpus callosum and mild generalized ventriculomegaly (PMID: 16650080) and cerebellar hypoplasia (PMID: 31474318). This variant has been identified and classified as pathogenic by diagnostic laboratories in ClinVar. (SP) 0906 - Segregation evidence for this variant is inconclusive. It has been identified in two brothers with hypoplastic corpus callosum and mild generalized ventriculomegaly (PMID: 16650080). It was also reported to have segregated in 4 affected males across multiple generations in a single family; however, data was not shown (PMID: 8929944). (I) 1007 - No published functional evidence has been identified for this variant. (I) 1205 - This variant has been shown to be maternally inherited (by quad analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
| Baylor Genetics | RCV000010683 | SCV001525999 | pathogenic | X-linked hydrocephalus syndrome | 2018-01-27 | criteria provided, single submitter | clinical testing | This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 8929944, 16650080] |
| Ce |
RCV001093004 | SCV001249773 | pathogenic | not provided | 2018-01-01 | criteria provided, single submitter | clinical testing | |
| University of Washington Center for Mendelian Genomics, |
RCV001257991 | SCV001434804 | likely pathogenic | Congenital cerebellar hypoplasia | no assertion criteria provided | research | ||
| Dobyns Lab, |
RCV000010684 | SCV000916343 | pathogenic | X-linked complicated corpus callosum dysgenesis | 2019-02-18 | no assertion criteria provided | research | |
| OMIM | RCV000010684 | SCV000030910 | pathogenic | X-linked complicated corpus callosum dysgenesis | 2006-05-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000010683 | SCV000030909 | pathogenic | X-linked hydrocephalus syndrome | 2006-05-01 | no assertion criteria provided | literature only |