ClinVar Miner

Submissions for variant NM_006306.4(SMC1A):c.3254A>G (p.Tyr1085Cys)

dbSNP: rs587784418
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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 RCV000147566 SCV000195014 pathogenic Congenital muscular hypertrophy-cerebral syndrome 2013-02-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000147566 SCV000637996 likely pathogenic Congenital muscular hypertrophy-cerebral syndrome 2020-04-07 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Family studies have shown that this variant co-segregates with disease in a family with features consistent with Cornelia de Lange syndrome (Invitae). This variant has been reported to be de novo in an individual affected with Cornelia de Lange syndrome. ClinVar contains an entry for this variant (Variation ID: 159956). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with cysteine at codon 1085 of the SMC1A protein (p.Tyr1085Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine.

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