ClinVar Miner

Submissions for variant NM_003036.4(SKI):c.2141G>A (p.Arg714His) (rs754486257)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197481 SCV000250662 likely benign not specified 2014-07-23 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000807347 SCV000947395 uncertain significance Shprintzen-Goldberg syndrome 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 714 of the SKI protein (p.Arg714His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. While this variant is present in population databases (rs754486257), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SKI-related disease. ClinVar contains an entry for this variant (Variation ID: 213679). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The histidine 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 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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