ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.4840C>T (p.Arg1614Trp)

dbSNP: rs1568565971
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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 RCV000703699 SCV000832613 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-03-07 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 1646 of the SMARCA4 protein (p.Arg1646Trp). This variant is not present in population databases (gnomAD no frequency). 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: 580225). 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 RCV001023295 SCV001185148 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-02 criteria provided, single submitter clinical testing The p.R1646W variant (also known as c.4936C>T), located in coding exon 34 of the SMARCA4 gene, results from a C to T substitution at nucleotide position 4936. The arginine at codon 1646 is replaced by tryptophan, an amino acid with dissimilar properties. 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 available evidence, the clinical significance of this variant remains unclear.
Genome-Nilou Lab RCV001809772 SCV002056998 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV001023295 SCV002535195 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-23 criteria provided, single submitter curation
PreventionGenetics, part of Exact Sciences RCV003403632 SCV004103942 uncertain significance SMARCA4-related disorder 2023-10-02 criteria provided, single submitter clinical testing The SMARCA4 c.4936C>T variant is predicted to result in the amino acid substitution p.Arg1646Trp. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Fulgent Genetics, Fulgent Genetics RCV005021093 SCV005653305 uncertain significance Rhabdoid tumor predisposition syndrome 2; Intellectual disability, autosomal dominant 16; Otosclerosis 12 2024-06-20 criteria provided, single submitter clinical testing

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