ClinVar Miner

Submissions for variant NM_006306.4(SMC1A):c.2132G>A (p.Arg711Gln)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001390824 SCV001592681 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2020-07-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 711 of the SMC1A protein (p.Arg711Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in individual(s) with Cornelia de Lange syndrome (PMID: 20358602). In at least one individual the variant was observed to be de novo. 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 determined to be pathogenic (PMID: 17273969). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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