ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.385G>A (p.Val129Ile) (rs201156403)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518403 SCV000614107 likely pathogenic not provided 2018-09-21 criteria provided, single submitter clinical testing Statistically enriched in uncharacterized patients compared to unmatched population data. Conflicting predictions of the effect on the protein. Located in potentially critical domain of the protein. Co-occurs with otherwise positive results less than expected.
Invitae RCV000638162 SCV000759648 uncertain significance Charcot-Marie-Tooth disease, type I 2019-12-15 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 129 of the MPZ protein (p.Val129Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MPZ-related disease. 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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