ClinVar Miner

Submissions for variant NM_152564.5(VPS13B):c.9968A>G (p.Tyr3323Cys)

gnomAD frequency: 0.00001  dbSNP: rs376549169
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001298886 SCV001487957 uncertain significance Cohen syndrome 2021-08-12 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. This sequence change replaces tyrosine with cysteine at codon 3348 of the VPS13B protein (p.Tyr3348Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs376549169, ExAC 0.001%). This variant has not been reported in the literature in individuals with VPS13B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Natera, Inc. RCV001298886 SCV002082728 uncertain significance Cohen syndrome 2020-03-11 no assertion criteria provided clinical testing

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