ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.422C>T (p.Ser141Leu)

gnomAD frequency: 0.00001  dbSNP: rs1060502073
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460860 SCV000548408 uncertain significance Rhabdoid tumor predisposition syndrome 2 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 141 of the SMARCA4 protein (p.Ser141Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SMARCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 408627). 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. 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.
Ambry Genetics RCV000563371 SCV000675147 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-28 criteria provided, single submitter clinical testing The p.S141L variant (also known as c.422C>T), located in coding exon 3 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 422. The serine at codon 141 is replaced by leucine, an amino acid with dissimilar properties. This variant has been detected in multiple individuals with no reported features of Coffin-Siris syndrome (Ambry internal data). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, the association of this alteration with rhabdoid tumor predisposition syndrome is unknown; however, the association of this alteration with Coffin-Siris syndrome is unlikely.
Fulgent Genetics, Fulgent Genetics RCV000764171 SCV000895173 uncertain significance Rhabdoid tumor predisposition syndrome 2; Intellectual disability, autosomal dominant 16 2018-10-31 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001809359 SCV002056309 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000460860 SCV005052746 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-02-16 criteria provided, single submitter clinical testing

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