ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.4569C>A (p.Asn1523Lys)

dbSNP: rs34389675
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000805476 SCV000945433 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-07-17 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1555 of the SMARCA4 protein (p.Asn1555Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 650343). 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) performed at Invitae indicates that this missense variant is not expected to disrupt SMARCA4 protein function with a negative predictive value of 95%. 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 RCV004949943 SCV005506423 uncertain significance Hereditary cancer-predisposing syndrome 2024-08-04 criteria provided, single submitter clinical testing The p.N1555K variant (also known as c.4665C>A), located in coding exon 32 of the SMARCA4 gene, results from a C to A substitution at nucleotide position 4665. The asparagine at codon 1555 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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