ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.4171G>A (p.Glu1391Lys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV001156789 SCV001318315 uncertain significance Usher syndrome, type 2C 2018-01-12 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195223 SCV001365530 uncertain significance not specified 2019-08-14 criteria provided, single submitter clinical testing The p.Glu139Lys variant in ADGRV1 has not been previously reported in individuals with Usher syndrone but has been identified in 0.2% (43/19396) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses 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: BS1_Supporting.
Invitae RCV001236644 SCV001409376 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1391 of the ADGRV1 protein (p.Glu1391Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs766007827, ExAC 0.2%). This variant has not been reported in the literature in individuals with ADGRV1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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