ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.404T>C (p.Ile135Thr) (rs121913587)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425572 SCV000521267 pathogenic not provided 2017-01-06 criteria provided, single submitter clinical testing The I135T missense variant has been reported previously in individuals with Charcot-Marie-Tooth disease type 1 and demyelinating peripheral neuropathy (Roa et al., 1996; Tyson et al., 1997; Mersiyanova et al. 2000). The I135T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I135T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants at the same position (I135L) and in nearby residues (P133S, D134N/G/E, V136E, G137S/V/A) have been reported in the Human Gene Mutation Database in association with MPZ-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein.
OMIM RCV000015235 SCV000035494 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 1996-01-01 no assertion criteria provided literature only

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