ClinVar Miner

Submissions for variant NM_032119.4(ADGRV1):c.14761G>A (p.Ala4921Thr) (rs200115167)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155116 SCV000204802 likely benign not specified 2013-04-24 criteria provided, single submitter clinical testing Ala4921Thr in exon 72 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 0.1% (8/8218) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs200115167). Furthermore, this amino acid is not well conserved acr oss species and several mammals carry a threonine (Thr) at this position.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000724660 SCV000232408 uncertain significance not provided 2015-03-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000155116 SCV001157334 uncertain significance not specified 2018-07-31 criteria provided, single submitter clinical testing The ADGRV1 c.14761G>A; p.Ala4921Thr variant (rs200115167), to our knowledge, has not been reported in the medical literature; however, it is listed in the ClinVar database with conflicting interpretations of pathogenicity (Variation ID: 178370). This variant is found in the general population with an allele frequency in non-Finnish European populations of 0.00% (101/128,320 alleles) in the Genome Aggregation Database. The alanine at codon 4921 is moderately conserved (Alamut v.2.11) and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. However, based on the available information, the clinical significance of this variant is uncertain.
Invitae RCV000724660 SCV001222928 uncertain significance not provided 2019-12-29 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 4921 of the ADGRV1 protein (p.Ala4921Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs200115167, ExAC 0.06%). This variant has not been reported in the literature in individuals with ADGRV1-related conditions. ClinVar contains an entry for this variant (Variation ID: 178370). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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