ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1456G>A (p.Val486Ile) (rs200717031)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000218491 SCV000272435 uncertain significance not specified 2015-08-11 criteria provided, single submitter clinical testing The p.Val486Ile variant in SKI has not been previously reported in individuals w ith Shprintzen-Goldberg syndrome, but has been identified in 1/216 Yoruba Africa n chromosomes by the 1000 Genomes Project (dbSNP rs200717031). Computational pre diction tools and conservation analysis do not provide strong support for or aga inst an impact to the protein. In summary, the clinical significance of the p.Va l486Ile variant is uncertain.
Invitae RCV000535528 SCV000637281 uncertain significance Shprintzen-Goldberg syndrome 2017-04-18 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 486 of the SKI protein (p.Val486Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. The frequency data for this variant (rs200717031) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 229252). 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 disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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