Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000861596 | SCV001001962 | likely benign | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000861596 | SCV001767751 | likely benign | not provided | 2021-03-31 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003396496 | SCV004122220 | uncertain significance | not specified | 2023-10-26 | criteria provided, single submitter | clinical testing | Variant summary: VPS13A c.6541G>A (p.Val2181Ile) results in a conservative amino acid change located in the Vacuolar protein sorting-associated protein 13, VPS13 adaptor binding domain (IPR009543) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 251296 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in VPS13A causing Choreoacanthocytosis (0.00033 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6541G>A in individuals affected with Choreoacanthocytosis and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as likely benign (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Prevention |
RCV003908162 | SCV004719037 | likely benign | VPS13A-related disorder | 2019-07-30 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |
Ambry Genetics | RCV004029300 | SCV004978102 | likely benign | Inborn genetic diseases | 2022-03-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Natera, |
RCV001274101 | SCV001457845 | uncertain significance | Chorea-acanthocytosis | 2020-01-24 | no assertion criteria provided | clinical testing |