ClinVar Miner

Submissions for variant NM_001281463.1(SMC1A):c.2065C>T (p.Arg689Trp) (rs587784409)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000147557 SCV000195004 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2013-02-08 criteria provided, single submitter clinical testing
Invitae RCV000147557 SCV001205364 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 711 of the SMC1A protein (p.Arg711Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs587784409, ExAC 0.02%). This variant has been observed in individual(s) with Cornelia de Lange syndrome (PMID: 17273969, 19701948). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 159947). 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 expected to disrupt SMC1A protein function. This variant disrupts the p.Arg711 amino acid residue in SMC1A. Other variant(s) that disrupt this residue have been observed in individuals with SMC1A-related conditions (PMID: 20358602), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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