ClinVar Miner

Submissions for variant NM_004447.6(EPS8):c.670G>A (p.Val224Ile)

gnomAD frequency: 0.00010  dbSNP: rs758506896
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825161 SCV000966433 likely benign not specified 2018-12-13 criteria provided, single submitter clinical testing The p.Val224Ile variant in EPS8 is classified as likely benign because the valin e at position 224 is not conserved through species, with 3 mammals (squirrel mon key, oppossum, wallaby) having an isoleucine. This variant has been identified i n 0.028% (10/35226) of Latino chromosomes by gnomAD (http://gnomad.broadinstitut e.org). ACMG/AMP criteria applied: BP4_Strong.
Labcorp Genetics (formerly Invitae), Labcorp RCV001856264 SCV002262581 uncertain significance not provided 2022-03-15 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 224 of the EPS8 protein (p.Val224Ile). This variant is present in population databases (rs758506896, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with EPS8-related conditions. ClinVar contains an entry for this variant (Variation ID: 666692). 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 isoleucine 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.
GeneDx RCV001856264 SCV002559437 uncertain significance not provided 2022-07-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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