ClinVar Miner

Submissions for variant NM_001281463.1(SMC1A):c.521G>A (p.Arg174His) (rs1556890815)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000639414 SCV000760988 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2017-10-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 196 of the SMC1A protein (p.Arg196His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Cornelia de Lange syndrome (PMID: 19701948), and in at least 2 individuals this variant was reported to arise de novo (PMID: 17273969, 17221863). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a rare missense change that has been reported as de novo in several affected individuals, for these reasons, this variant has been classified as Pathogenic.

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