ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1258G>A (p.Ala420Thr) (rs771862077)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507645 SCV000605111 uncertain significance not specified 2016-09-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618333 SCV000739617 likely benign Cardiovascular phenotype 2017-06-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification
Invitae RCV000205977 SCV000261638 uncertain significance Shprintzen-Goldberg syndrome 2018-08-14 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 420 of the SKI protein (p.Ala420Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs771862077, ExAC 0.01%) but has not been reported in the literature in individuals with a SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 220793). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, 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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