ClinVar Miner

Submissions for variant NM_033305.3(VPS13A):c.398C>T (p.Pro133Leu)

gnomAD frequency: 0.00009  dbSNP: rs202090510
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000516181 SCV000616246 uncertain significance not specified 2017-02-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002527557 SCV003008766 uncertain significance not provided 2022-08-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 133 of the VPS13A protein (p.Pro133Leu). This variant is present in population databases (rs202090510, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with VPS13A-related conditions. ClinVar contains an entry for this variant (Variation ID: 448860). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000516181 SCV005725942 uncertain significance not specified 2024-11-01 criteria provided, single submitter clinical testing Variant summary: VPS13A c.398C>T (p.Pro133Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 249580 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in VPS13A causing Choreoacanthocytosis (0.00028 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.398C>T in individuals affected with Choreoacanthocytosis and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 448860). Based on the evidence outlined above, the variant was classified as uncertain significance.

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