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 2020-08-26 criteria provided, single submitter clinical testing This variant has been identified in at least one individual with clinical features associated with this gene. In our internal patient population, this variant is statistically more frequent than in the general population, which is weak evidence this variant may be disease causing (http://gnomad.broadinstitute.org). This variant occurs as the most likely explanation for disease in a significant number of internal cases, suggesting this variant is associated with disease. The variant is located in a region that is considered important for protein function and/or structure
Invitae RCV000638162 SCV000759648 uncertain significance Charcot-Marie-Tooth disease, type I 2020-08-30 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 conditions. ClinVar contains an entry for this variant (Variation ID: 447729). 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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