Submissions for variant NM_003073.5(SMARCB1):c.568C>T (p.Arg190Trp)

dbSNP: rs1601405064

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001024411	SCV001186424	uncertain significance	Hereditary cancer-predisposing syndrome	2019-07-22	criteria provided, single submitter	clinical testing	The p.R190W variant (also known as c.568C>T), located in coding exon 5 of the SMARCB1 gene, results from a C to T substitution at nucleotide position 568. The arginine at codon 190 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001195823	SCV001366243	likely pathogenic	SMARCB1-related schwannomatosis	2018-11-26	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS2,PM2,PP3.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001365280	SCV001561545	uncertain significance	not provided	2024-05-07	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 190 of the SMARCB1 protein (p.Arg190Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 825898). 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 SMARCB1 protein function with a positive predictive value of 80%. 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.
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003127587	SCV003804047	likely pathogenic	Autism spectrum disorder	2022-04-13	criteria provided, single submitter	clinical testing