ClinVar Miner

Submissions for variant NM_153717.3(EVC):c.1777G>A (p.Val593Met)

gnomAD frequency: 0.00014  dbSNP: rs150535483
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002071 SCV001159908 uncertain significance not specified 2018-09-05 criteria provided, single submitter clinical testing The EVC c.1777G>A; p.Val593Met variant (rs150535483), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found on eight chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The valine at codon 593 is moderately conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, this variant may impact splicing by weakening the nearby canonical splice acceptor site of exon 13, though mRNA studies would be required to confirm this. Given the lack of clinical and functional data, the significance of the p.Val593Met variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001860509 SCV002217824 uncertain significance Ellis-van Creveld syndrome; Curry-Hall syndrome 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 593 of the EVC protein (p.Val593Met). This variant is present in population databases (rs150535483, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with EVC-related conditions. ClinVar contains an entry for this variant (Variation ID: 811749). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Natera, Inc. RCV001273624 SCV001456832 uncertain significance Ellis-van Creveld syndrome 2020-09-16 no assertion criteria provided clinical testing

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