ClinVar Miner

Submissions for variant NM_001128849.2(SMARCA4):c.407C>T (p.Ala136Val) (rs535299273)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000548772 SCV000648087 uncertain significance Rhabdoid tumor predisposition syndrome 2 2019-12-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 136 of the SMARCA4 protein (p.Ala136Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs535299273, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SMARCA4-related disease. ClinVar contains an entry for this variant (Variation ID: 470381). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000568449 SCV000664125 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-26 criteria provided, single submitter clinical testing Insufficient evidence
Fulgent Genetics,Fulgent Genetics RCV000764170 SCV000895172 uncertain significance Rhabdoid tumor predisposition syndrome 2; Mental retardation, autosomal dominant 16 2018-10-31 criteria provided, single submitter clinical testing

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