ClinVar Miner

Submissions for variant NM_001303256.3(MORC2):c.1447C>G (p.Leu483Val)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814817 SCV000955244 uncertain significance Charcot-Marie-Tooth disease, axonal, type 2z 2018-08-20 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 421 of the MORC2 protein (p.Leu421Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MORC2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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