ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.15169C>T (p.Pro5057Ser) (rs183633457)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725653 SCV000338383 uncertain significance not provided 2016-01-26 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000377249 SCV000711059 uncertain significance not specified 2019-09-13 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro5057Ser variant in ADGRV1 has been previously reported in 2 individuals with hearing loss by our laboratory, including 1 who was compound heterozygous for a second variant of uncertain significance in ADGRV1. This variant has been identified in 0.09% (117/128212) of European 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, while the clinical significance of this variant is uncertain, its frequency suggests that it is more likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
Fulgent Genetics,Fulgent Genetics RCV000765858 SCV000897254 uncertain significance Usher syndrome, type 2C; Febrile seizures, familial, 4 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000725653 SCV001224325 uncertain significance not provided 2020-01-15 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 5057 of the ADGRV1 protein (p.Pro5057Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs183633457, ExAC 0.1%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 285387). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.
Illumina Clinical Services Laboratory,Illumina RCV001153318 SCV001314602 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.

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