ClinVar Miner

Submissions for variant NM_014140.3(SMARCAL1):c.1727T>C (p.Ile576Thr) (rs138819354)

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 RCV000489879 SCV000576865 uncertain significance not provided 2017-04-17 criteria provided, single submitter clinical testing The I576T variant in the SMARCAL1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I576T variant is observed in 14/10400 (0.13%) alleles from individuals of African background, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I576T 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 where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I576T as a variant of uncertain significance.
Invitae RCV000814798 SCV000955225 uncertain significance Schimke immunoosseous dysplasia 2018-11-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 576 of the SMARCAL1 protein (p.Ile576Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs138819354, ExAC 0.1%). This variant has not been reported in the literature in individuals with SMARCAL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 426426). 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: "Deleterious"; 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.