ClinVar Miner

Submissions for variant NM_147127.5(EVC2):c.809C>T (p.Ser270Leu)

gnomAD frequency: 0.00011  dbSNP: rs369153874
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521574 SCV000621221 uncertain significance not provided 2017-09-26 criteria provided, single submitter clinical testing The S270L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. S270L is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The S270L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV002528272 SCV003230521 uncertain significance Ellis-van Creveld syndrome; Curry-Hall syndrome 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 270 of the EVC2 protein (p.Ser270Leu). This variant is present in population databases (rs369153874, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EVC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452413). 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 leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV003278869 SCV003970958 uncertain significance Inborn genetic diseases 2023-05-31 criteria provided, single submitter clinical testing The c.809C>T (p.S270L) alteration is located in exon 6 (coding exon 6) of the EVC2 gene. This alteration results from a C to T substitution at nucleotide position 809, causing the serine (S) at amino acid position 270 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004751581 SCV005346650 uncertain significance EVC2-related disorder 2024-07-08 no assertion criteria provided clinical testing The EVC2 c.809C>T variant is predicted to result in the amino acid substitution p.Ser270Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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