Submissions for variant NM_004385.5(VCAN):c.8919G>T (p.Gln2973His)

dbSNP: rs145612319

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001229696	SCV001402150	uncertain significance	not provided	2024-11-05	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 2973 of the VCAN protein (p.Gln2973His). This variant is present in population databases (rs145612319, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with VCAN-related conditions. ClinVar contains an entry for this variant (Variation ID: 956818). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
PreventionGenetics, part of Exact Sciences	RCV003953591	SCV004775201	uncertain significance	VCAN-related disorder	2024-02-21	no assertion criteria provided	clinical testing	The VCAN c.8919G>T variant is predicted to result in the amino acid substitution p.Gln2973His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.059% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which may be too common to be an undocumented cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.