Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238812 | SCV005885121 | uncertain significance | not specified | 2024-12-18 | criteria provided, single submitter | clinical testing | Variant summary: IFT140 c.3955_3960delGCCAAG (p.Ala1319_Lys1320del) results in an in-frame deletion that is predicted to remove two amino acids from the encoded protein. The variant allele was found at a frequency of 0.002 in 1607122 control chromosomes in the gnomAD database, including 8 homozygotes, providing evidence for a benign role. However, c.3955_3960delGCCAAG has been reported in the literature in a homozygous stillborn individual affected with Jeune Asphyxiating Thoracic Dystrophy (e.g. Shaheen_2016, Shamseldin_2021) or in individuals affected with retinitis pigmentosa or an unspecified retinal disease as a heterozygous or unreported genotype (e.g. Sergouniotis_2016, AlBdour_2020, Perea-Romero_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Asphyxiating Thoracic Dystrophy 1. 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: 32587456, 34448047, 27628848, 27894351, 34645488). ClinVar contains an entry for this variant (Variation ID: 266103). Based on the conflicting evidence outlined above, the variant was classified as uncertain significance. |
| Institute of Human Genetics, |
RCV004816468 | SCV005071616 | uncertain significance | Retinal dystrophy | 2023-01-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004021042 | SCV004886193 | uncertain significance | Inborn genetic diseases | 2023-12-12 | criteria provided, single submitter | clinical testing | The c.3955_3960delGCCAAG (p.A1319_K1320del) alteration is located in exon 29 (coding exon 27) of the IFT140 gene. This alteration consists of an in-frame deletion of 6 nucleotides between nucleotide positions c.3955 and c.3960, resulting in the deletion of 2 residues. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Genomic Medicine Center of Excellence, |
RCV000386105 | SCV004810155 | uncertain significance | Saldino-Mainzer syndrome | 2024-04-04 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000386105 | SCV001417925 | benign | Saldino-Mainzer syndrome | 2025-01-29 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000386105 | SCV000395076 | uncertain significance | Saldino-Mainzer syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV004752816 | SCV005344621 | uncertain significance | IFT140-related disorder | 2024-04-04 | no assertion criteria provided | clinical testing | The IFT140 c.3955_3960del6 variant is predicted to result in an in-frame deletion (p.Ala1319_Lys1320del). This variant was reported in the homozygous state in an individual with short-rib thoracic dysplasia/oral-facial-digital syndrome (Patient 12DG1103, Table S3, Shaheen et al. 2016. PubMed ID: 27894351; Table S1, Shamseldin et al. 2021. PubMed ID: 34645488). This variant is reported in 0.36% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, including one homozygote. This variant has been reported in ClinVar with conflicting interpretations of likely pathogenic (1), uncertain (4), and benign (1) (https://www.ncbi.nlm.nih.gov/clinvar/variation/266103/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001795477 | SCV002038205 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Laboratory of Diagnostic Genome Analysis, |
RCV001795477 | SCV002035672 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Clinical Genetics, |
RCV001795477 | SCV002034619 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Genomic Medicine Center of Excellence, |
RCV000256471 | SCV000322798 | likely pathogenic | Orofacial-digital syndrome III; Asphyxiating thoracic dystrophy 1 | no assertion criteria provided | research |