Submissions for variant NM_014140.4(SMARCAL1):c.2291G>A (p.Arg764Gln)

gnomAD frequency: 0.00002  dbSNP: rs267607071

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000004395	SCV000957039	pathogenic	Schimke immuno-osseous dysplasia	2024-10-30	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 764 of the SMARCAL1 protein (p.Arg764Gln). This variant is present in population databases (rs267607071, gnomAD 0.006%). This missense change has been observed in individual(s) with Schimke immuno-osseous dysplasia (PMID: 11799392, 22998683). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 4178). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SMARCAL1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SMARCAL1 function (PMID: 18805831, 18974355, 19793864, 23671665, 26089390). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000004395	SCV005368400	pathogenic	Schimke immuno-osseous dysplasia	2019-07-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000004395	SCV005648213	pathogenic	Schimke immuno-osseous dysplasia	2024-03-20	criteria provided, single submitter	clinical testing
OMIM	RCV000004395	SCV000024567	pathogenic	Schimke immuno-osseous dysplasia	2009-10-15	no assertion criteria provided	literature only