Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005418069 | SCV006086420 | likely benign | not specified | 2025-05-14 | criteria provided, single submitter | clinical testing | Variant summary: ABCC8 c.1958G>A (p.Arg653Gln) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 0.00058 in 250960 control chromosomes, predominantly at a frequency of 0.0044 within the South Asian subpopulation in the gnomAD database, including one homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 1.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC8 causing Familial Hyperinsulinism phenotype (0.0034). ClinVar contains an entry for this variant (Variation ID: 303779). Based on the evidence outlined above, the variant was classified as likely benign. |
| Ce |
RCV000876083 | SCV004701919 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000876083 | SCV002027850 | uncertain significance | not provided | 2021-05-17 | criteria provided, single submitter | clinical testing | Observed in a patient with transient neonatal diabetes in published literature (Jahnavi et al., 2013); Published functional studies demonstrate the variant results in increased channel activity (Balamurugan et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22831748, 30861254) |
| Labcorp Genetics |
RCV000876083 | SCV001018600 | benign | not provided | 2024-08-28 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000321571 | SCV000369352 | likely benign | Permanent neonatal diabetes mellitus | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
| Illumina Laboratory Services, |
RCV000264134 | SCV000369351 | benign | Diabetes mellitus, transient neonatal, 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Illumina Laboratory Services, |
RCV000375215 | SCV000369350 | uncertain significance | Hyperinsulinemic hypoglycemia, familial, 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Natera, |
RCV001274299 | SCV001458271 | likely benign | Hereditary hyperinsulinism | 2020-01-23 | no assertion criteria provided | clinical testing |