ClinVar Miner

Submissions for variant NM_003072.5(SMARCA4):c.2783T>C (p.Leu928Pro)

dbSNP: rs1555778801
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575564 SCV000664201 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-04 criteria provided, single submitter clinical testing The p.L928P variant (also known as c.2783T>C), located in coding exon 18 of the SMARCA4 gene, results from a T to C substitution at nucleotide position 2783. The leucine at codon 928 is replaced by proline, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 30000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000703627 SCV000832535 uncertain significance Rhabdoid tumor predisposition syndrome 2 2018-11-14 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMARCA4-related disease. ClinVar contains an entry for this variant (Variation ID: 480625). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 928 of the SMARCA4 protein (p.Leu928Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
Genome-Nilou Lab RCV001809587 SCV002056847 uncertain significance Intellectual disability, autosomal dominant 16 2021-07-15 criteria provided, single submitter clinical testing

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