ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.326C>T (p.Pro109Leu)

gnomAD frequency: 0.00001  dbSNP: rs763471007
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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 RCV000204032 SCV000261933 uncertain significance Rhabdoid tumor predisposition syndrome 2 2024-12-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 109 of the SMARCA4 protein (p.Pro109Leu). This variant is present in population databases (rs763471007, 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: 220949). Invitae Evidence 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 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 RCV000569219 SCV000663931 likely benign Hereditary cancer-predisposing syndrome 2021-12-30 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome-Nilou Lab RCV001808569 SCV002056294 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002500660 SCV002784894 uncertain significance Rhabdoid tumor predisposition syndrome 2; Intellectual disability, autosomal dominant 16 2022-04-04 criteria provided, single submitter clinical testing
Mendelics RCV005230086 SCV005880298 uncertain significance Hereditary cancer 2025-02-26 criteria provided, single submitter clinical testing The available evidence is insufficient to conclusively determine the role of this variant. Therefore, it is classified as a Variant of Uncertain Significance.

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