Submissions for variant NM_170665.4(ATP2A2):c.392G>A (p.Arg131Gln)

dbSNP: rs121912738

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001729353	SCV004296217	pathogenic	not provided	2023-12-25	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 131 of the ATP2A2 protein (p.Arg131Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Darier disease (PMID: 10441323, 11168576, 12072062, 28035777). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17800). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP2A2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects ATP2A2 function (PMID: 16766529). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000019378	SCV000039668	pathogenic	Keratosis follicularis	2002-06-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001729353	SCV001978614	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001729353	SCV001979757	pathogenic	not provided		no assertion criteria provided	clinical testing