Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002044043 | SCV002114762 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with methionine at codon 2775 of the VPS13A protein (p.Lys2775Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine. This variant is present in population databases (rs760798467, ExAC 0.09%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with VPS13A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 | RCV002543503 | SCV003727114 | uncertain significance | Inborn genetic diseases | 2021-11-08 | criteria provided, single submitter | clinical testing | The c.8324A>T (p.K2775M) alteration is located in exon 60 (coding exon 60) of the VPS13A gene. This alteration results from a A to T substitution at nucleotide position 8324, causing the lysine (K) at amino acid position 2775 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
3billion | RCV004720323 | SCV005328974 | likely benign | Chorea-acanthocytosis | 2024-09-20 | criteria provided, single submitter | clinical testing | The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. |