Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001044689 | SCV001208496 | likely benign | not provided | 2025-01-13 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001155718 | SCV001317173 | uncertain significance | Usher syndrome type 2C | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797816 | SCV002041784 | uncertain significance | not specified | 2021-11-30 | criteria provided, single submitter | clinical testing | Variant summary: ADGRV1 c.12335T>G (p.Leu4112Trp) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 domain (IPR003644) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 248542 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in ADGRV1 causing Usher Syndrome (0.0001 vs 0.0054), allowing no conclusion about variant significance. c.12335T>G has been reported in the literature in one sporadic, late onset hearing loss patient (Miyagawa_2013). This report does not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Fulgent Genetics, |
RCV002505575 | SCV002812653 | uncertain significance | Usher syndrome type 2C; Febrile seizures, familial, 4 | 2021-07-30 | criteria provided, single submitter | clinical testing |