ClinVar Miner

Submissions for variant NM_004447.6(EPS8):c.1903G>A (p.Val635Ile)

gnomAD frequency: 0.00046  dbSNP: rs145722981
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001581895 SCV001818039 likely benign not provided 2021-07-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002573312 SCV003703638 uncertain significance Inborn genetic diseases 2022-05-25 criteria provided, single submitter clinical testing The c.1903G>A (p.V635I) alteration is located in exon 18 (coding exon 17) of the EPS8 gene. This alteration results from a G to A substitution at nucleotide position 1903, causing the valine (V) at amino acid position 635 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001581895 SCV005736013 uncertain significance not provided 2024-08-01 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 635 of the EPS8 protein (p.Val635Ile). This variant is present in population databases (rs145722981, gnomAD 0.2%). 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: 1214161). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt EPS8 protein function with a negative predictive value of 80%. 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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