ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.362A>G (p.Asp121Gly) (rs1571818953)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000814912 SCV000955350 uncertain significance Charcot-Marie-Tooth disease, type I 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 121 of the MPZ protein (p.Asp121Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Asp121 amino acid residue in MPZ. Other variant(s) that disrupt this residue have been observed in individuals with MPZ-related conditions (PMID:27774063), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.
CMT Laboratory,Bogazici University RCV001353168 SCV001548329 uncertain significance Charcot-Marie-Tooth disease, demyelinating, type 1b 2020-12-01 criteria provided, single submitter clinical testing
Genesis Genome Database RCV000814912 SCV000999691 uncertain significance Charcot-Marie-Tooth disease, type I 2019-08-14 no assertion criteria provided research

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