ClinVar Miner

Submissions for variant NM_014363.6(SACS):c.9292A>G (p.Ile3098Val) (rs745664974)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227902 SCV000289964 uncertain significance Spastic paraplegia 2016-01-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 3098 of the SACS protein (p.Ile3098Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs745664974, ExAC <0.01%) but has not been reported in the literature in individuals with a SACS-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Furthermore, the valine amino acid residue is found in multiple mammalian species, which also suggests that this missense change does not adversely affect protein function. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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