ClinVar Miner

Submissions for variant NM_153717.3(EVC):c.1528G>A (p.Val510Ile) (rs143971158)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000378158 SCV000450267 uncertain significance Ellis-van Creveld syndrome 2018-01-13 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.
Illumina Clinical Services Laboratory,Illumina RCV000283807 SCV000450268 likely benign Curry-Hall syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000613661 SCV000720055 likely benign not specified 2017-06-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756095 SCV000883811 likely benign not provided 2017-06-30 criteria provided, single submitter clinical testing The p.Val510Ile variant (rs143971158) has not been reported in the medical literature but it has been reported to ClinVar (Variation ID 349181). The p.Val510Ile variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.6 percent in European (Finnish) population (identified on 152 out of 25,400 chromosomes, no homozygotes), and corresponding calculated carrier frequency of 1.2 percent. The estimated carrier frequency in general population, based on the estimated incidence of Ellis-van Creveld syndrome of 1 in 60,000 (D’Asdia 2013), would be approximately 0.8 percent. Thus, the calculated carrier frequency of 1.2 percent for this variant is about thirty percent greater than the estimated general carrier frequency of 0.8 for Ellis-van Creveld syndrome. The valine at position 510 is weakly conserved (Alamut software v2.9.0) with isoleucine present in several mammals including bush-baby and dog. Computational analyses of the effects of the variant on protein structure and function indicates neutral effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Altogether, based on the available evidence, we classified the p.Val510Ile variant as likely benign.
Invitae RCV001080199 SCV001091626 likely benign Ellis-van Creveld syndrome; Curry-Hall syndrome 2019-12-31 criteria provided, single submitter clinical testing

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