ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.1384C>G (p.Pro462Ala) (rs199797772)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621055 SCV000738430 uncertain significance Cardiovascular phenotype 2016-07-12 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Insufficient or conflicting evidence,In silico models in agreement (benign)
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658485 SCV000780253 likely benign not provided 2018-02-28 criteria provided, single submitter clinical testing
Invitae RCV000467693 SCV000550379 uncertain significance Shprintzen-Goldberg syndrome 2018-09-26 criteria provided, single submitter clinical testing This sequence change replaces proline with alanine at codon 462 of the SKI protein (p.Pro462Ala). The proline residue is moderately conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs199797772, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 409974). 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 and their clinical significance is uncertain. 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.

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