ClinVar Miner

Submissions for variant NM_003073.5(SMARCB1):c.1115C>T (p.Thr372Met)

gnomAD frequency: 0.00001  dbSNP: rs992198711
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000539836 SCV000638743 uncertain significance not provided 2023-04-15 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 SMARCB1 protein function. ClinVar contains an entry for this variant (Variation ID: 464321). This variant has not been reported in the literature in individuals affected with SMARCB1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 372 of the SMARCB1 protein (p.Thr372Met).
Ambry Genetics RCV000561787 SCV000675218 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-16 criteria provided, single submitter clinical testing The p.T372M variant (also known as c.1115C>T), located in coding exon 8 of the SMARCB1 gene, results from a C to T substitution at nucleotide position 1115. The threonine at codon 372 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Missense and in-frame variants in SMARCB1 are known to cause neurodevelopmental disorders; however, such associations with rhabdoid tumor predisposition syndrome are exceedingly rare (Kosho T et al. Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):262-75; Eaton KW et al. Pediatr Blood Cancer. 2011 Jan;56(1):7-15). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005027639 SCV005660984 uncertain significance SMARCB1-related schwannomatosis; Rhabdoid tumor predisposition syndrome 1; Intellectual disability, autosomal dominant 15 2024-04-18 criteria provided, single submitter clinical testing

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