ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.90C>G (p.Ile30Met) (rs770546306)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000201151 SCV000255804 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-06-17 criteria provided, single submitter clinical testing
Invitae RCV000464045 SCV000552942 pathogenic Charcot-Marie-Tooth disease, type I 2019-05-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 30 of the MPZ protein (p.Ile30Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Charcot-Marie-Tooth disease, type 1B and has been reported to segregate in affected families (PMID: 7694726, 26454100, Invitae database). ClinVar contains an entry for this variant (Variation ID: 217235). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Different missense substitution at this codon (p.Ile30Phe, p.Ile30Ser, p.Ile30Thr) have been identified in individuals affected with Dejerine Sottas disease and Charcot-Marie-Tooth disease (PMID: 17143884, 19259128, 20461396). This suggests that the isoleucine residue may be critical for MPZ protein function. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000712322 SCV000842788 pathogenic not provided 2015-06-17 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789438 SCV000928793 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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