ClinVar Miner

Submissions for variant NM_001128225.3(SLC39A13):c.640A>G (p.Ile214Val) (rs750123189)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519189 SCV000621669 uncertain significance not provided 2017-10-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the he SLC39A13 gene. The I214V variant has not been published as pathogenic or been reported as benign to our knowledge. The I214V variant is observed in 6/111342 (0.005%) alleles from individuals of European (non-Finnish) background in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). The I214V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved and valine (V) is the wild-type amino acid at this position in multiple species. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000526937 SCV000646926 uncertain significance Spondylocheirodysplasia, Ehlers-Danlos syndrome-like 2018-12-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 214 of the SLC39A13 protein (p.Ile214Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs750123189, ExAC 0.006%) but has not been reported in the literature in individuals with a SLC39A13-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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