Submissions for variant NM_032119.4(ADGRV1):c.5785G>T (p.Ala1929Ser) (rs41311335)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000039596	SCV000063285	likely benign	not specified	2013-06-11	criteria provided, single submitter	clinical testing	Ala1929Ser in exon 28 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.1% (9/8264) of European American chromosomes and 0.02% (1/3876) of African American chromosomes in a broad popula tion by the NHLBI Exome sequencing project (http://evs.gs.washington.edu/EVS/; d bSNP rs41311335). In addition, this variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals and co mputational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likeliho od of impact to the protein.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000723976	SCV000228648	uncertain significance	not provided	2014-06-26	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000723976	SCV001142935	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV000723976	SCV001217507	uncertain significance	not provided	2020-10-20	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with serine at codon 1929 of the ADGRV1 protein (p.Ala1929Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs41311335, ExAC 0.1%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 46340). 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: Tolerated; PolyPhen-2: Probably 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.
Illumina Clinical Services Laboratory,Illumina	RCV001151458	SCV001312585	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.
GeneDx	RCV000723976	SCV001792084	likely benign	not provided	2021-02-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22135276)