ClinVar Miner

Submissions for variant NM_006306.4(SMC1A):c.1486C>T (p.Arg496Cys)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001043421 SCV001207167 likely pathogenic Congenital muscular hypertrophy-cerebral syndrome 2019-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 496 of the SMC1A protein (p.Arg496Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical features of Cornelia de Lange syndrome (PMID: 17273969, Invitae). This variant has been reported to affect SMC1A protein function (PMID:18996922). This variant disrupts the p.Arg496 amino acid residue in SMC1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22140011, 24461912, 17273969). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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