Submissions for variant NM_003072.5(SMARCA4):c.1694C>T (p.Thr565Met)

dbSNP: rs1600082359

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001012774	SCV001173270	uncertain significance	Hereditary cancer-predisposing syndrome	2019-11-18	criteria provided, single submitter	clinical testing	The p.T565M variant (also known as c.1694C>T), located in coding exon 9 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 1694. The threonine at codon 565 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001220485	SCV001392477	uncertain significance	Rhabdoid tumor predisposition syndrome 2	2023-04-07	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMARCA4 protein function. ClinVar contains an entry for this variant (Variation ID: 819862). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 565 of the SMARCA4 protein (p.Thr565Met).
Genome-Nilou Lab	RCV001809903	SCV002056443	uncertain significance	Intellectual disability, autosomal dominant 16	2021-07-15	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University Hospital Muenster	RCV004584415	SCV002577986	likely pathogenic	See cases	2021-12-16	criteria provided, single submitter	clinical testing	ACMG categories: PS2,PM2,PP3