ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.13772C>T (p.Thr4591Ile)

gnomAD frequency: 0.00006  dbSNP: rs369108080
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001073997 SCV001239563 uncertain significance Retinal dystrophy 2018-10-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV001195220 SCV001365527 uncertain significance not specified 2019-05-21 criteria provided, single submitter clinical testing The p.Thr4591Ile variant in ADGRV1 has not been previously reported in individuals with hearing loss but has been identified in 0.01% (13/128070) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001306737 SCV001496118 likely benign not provided 2024-11-19 criteria provided, single submitter clinical testing
GeneDx RCV001306737 SCV002571624 uncertain significance not provided 2022-09-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001195220 SCV005204325 uncertain significance not specified 2024-06-13 criteria provided, single submitter clinical testing Variant summary: ADGRV1 c.13772C>T (p.Thr4591Ile) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 (IPR003644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 248824 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in ADGRV1 causing ADGRV1-Related Disorders, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.13772C>T in individuals affected with ADGRV1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 866190). Based on the evidence outlined above, the variant was classified as uncertain significance.

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