ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.1327G>C (p.Val443Leu) (rs765958389)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217206 SCV000280005 uncertain significance not provided 2016-03-31 criteria provided, single submitter clinical testing The V443L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V443L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000545532 SCV000657937 uncertain significance Charcot-Marie-Tooth disease type 4 2018-05-22 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 443 of the SBF2 protein (p.Val443Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs765958389, ExAC 0.006%) but has not been reported in the literature in individuals with a SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 234917). 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but 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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