Submissions for variant NM_152564.5(VPS13B):c.5902T>C (p.Cys1968Arg)

gnomAD frequency: 0.00001  dbSNP: rs1422533086

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001304058	SCV001493325	uncertain significance	Cohen syndrome	2020-03-10	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine with arginine at codon 1993 of the VPS13B protein (p.Cys1993Arg). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: Not Available; PolyPhen-2: Probably Damaging; Align-GVGD: Not Available). 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572907	SCV001797999	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001572907	SCV001922773	uncertain significance	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001304058	SCV002082594	uncertain significance	Cohen syndrome	2021-09-28	no assertion criteria provided	clinical testing