ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.1351C>T (p.Arg451Cys)

dbSNP: rs2086534839
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206436 SCV001377744 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 451 of the SMARCA4 protein (p.Arg451Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Coffin–Siris syndrome (PMID: 29095814, 32686290). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 937431). 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.
Baylor Genetics RCV001335684 SCV001528905 likely pathogenic Intellectual disability, autosomal dominant 16 2018-01-02 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Baylor Genetics RCV001533106 SCV001748926 likely pathogenic SMARCA4-related BAFopathy 2021-06-10 criteria provided, single submitter clinical testing
GeneDx RCV001655701 SCV001871004 pathogenic not provided 2023-04-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29095814, 32686290)
Genome-Nilou Lab RCV001335684 SCV002056160 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
Mendelics RCV001206436 SCV002519790 pathogenic Rhabdoid tumor predisposition syndrome 2 2022-05-04 criteria provided, single submitter clinical testing

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