ClinVar Miner

Submissions for variant NM_001281463.1(SMC1A):c.3112G>A (p.Glu1038Lys) (rs1057521921)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000427470 SCV000525071 likely pathogenic not provided 2016-03-11 criteria provided, single submitter clinical testing The E1060K variant in the SMC1A gene has been reported previously in the hemizygous state in one male child with developmental delay, dysmorphic facial features, clinodactyly, short stature, and a clinical diagnosis of Cornelia de Lange syndrome. The E1060K variant was present in the heterozygous state in that individual's mother, sister, and maternal grandmother, all of whom had mild intellectual disability (Jang et al., 2015). The E1060K variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E1060K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The E1060K variant is a strong candidate for a pathogenic variant.
Invitae RCV001066009 SCV001231002 uncertain significance Congenital muscular hypertrophy-cerebral syndrome 2019-02-02 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 1060 of the SMC1A protein (p.Glu1060Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with Cornelia de Lange syndrome and/or intellectual disability in a family (PMID: 26354354). ClinVar contains an entry for this variant (Variation ID: 384321). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.