ClinVar Miner

Submissions for variant NM_001281463.1(SMC1A):c.1421G>A (p.Arg474His) (rs122454123)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV000012441 SCV000747077 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2018-03-08 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000012441 SCV001368008 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2019-03-06 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP2,PP3.
Invitae RCV000012441 SCV001592682 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2020-05-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 496 of the SMC1A protein (p.Arg496His). The arginine residue is highly 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 observed in individual(s) with Cornelia de Lange syndrome (PMID: 17273969, 24461912, 22140011). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 11675). 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 (Invitae). 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.
GeneDx RCV001577833 SCV001805299 pathogenic not provided 2021-02-05 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28835994, 28548707, 30158690, 24461912, 22581668, 17273969, 19262687, 20583156, 26725122, 19701948, 18996922, 22140011)
OMIM RCV000012441 SCV000032675 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2009-02-01 no assertion criteria provided literature only

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