ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.1180del (p.Ser394fs)

dbSNP: rs1400695342
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Mass General Brigham Personalized Medicine RCV000825554 SCV000966872 pathogenic Rare genetic deafness 2018-04-05 criteria provided, single submitter clinical testing The p.Ser394fs variant in ADGRV1 has not been previously reported in individuals with Usher syndrome. This variant was present in 2/108680 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org); h owever, its frequency is low enough to be consistent with a recessive carrier fr equency. This variant is predicted to cause a frameshift, which alters the prote in?s amino acid sequence beginning at position 394 and leads to a premature term ination codon 12 amino acids downstream. This alteration is then predicted to le ad to a truncated or absent protein. Loss of function of the ADGRV1 gene is an e stablished disease mechanism for Usher syndrome. Furthermore, the presence of th is variant in trans with a pathogenic variant in an individual with hearing loss supports pathogenicity for the p.Ser394fs variant. In summary, this variant mee ts criteria to be classified as pathogenic for autosomal recessive Usher syndrom e based upon the predicted impact of the variant, low frequency in the general p opulation and presence in trans with a pathogenic variant. ACMG/AMP Criteria app lied: PVS1, PM2, PM3.
GeneDx RCV001008515 SCV001168287 likely pathogenic not provided 2020-12-09 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001008515 SCV002231125 pathogenic not provided 2021-06-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser394Hisfs*12) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 26667666, 30029497, 32467589). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 666991). For these reasons, this variant has been classified as Pathogenic.

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