ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.292C>T (p.Arg98Cys)

gnomAD frequency: 0.00001  dbSNP: rs121913590
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000015238 SCV000255799 pathogenic Charcot-Marie-Tooth disease type 1B 2013-11-06 criteria provided, single submitter clinical testing
GeneDx RCV000237048 SCV000292963 pathogenic not provided 2022-06-06 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect; R98C results in reduced transport of the MPZ protein to the plasma membrane (Lee et al., 2010; Saporta et al., 2012).; Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 12477701, 23250879, 9168174, 9187667, 20461396, 19293842, 8816708, 8797476, 17172621, 10093067, 8644725, 21840889, 28704293, 29687021, 15050444, 10207934, 31211173, 31827005, 33825325, 26310628, 24077912, 22689911)
Invitae RCV000548074 SCV000636242 pathogenic Charcot-Marie-Tooth disease, type I 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 98 of the MPZ protein (p.Arg98Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease and Dejerine-Sottas syndrome (PMID: 8644725, 8797476, 9168174, 20461396, 21840889). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 14175). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MPZ protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects MPZ function (PMID: 20461396, 22689911). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000015238 SCV001521544 pathogenic Charcot-Marie-Tooth disease type 1B 2020-05-21 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000015238 SCV003807071 pathogenic Charcot-Marie-Tooth disease type 1B 2022-06-05 criteria provided, single submitter clinical testing ACMG classification criteria: PS3 supporting, PS4 strong, PM2 moderated, PM5 moderated, PM6 strong, PP3 supporting
CeGaT Center for Human Genetics Tuebingen RCV000237048 SCV004704293 pathogenic not provided 2024-02-01 criteria provided, single submitter clinical testing MPZ: PS2, PM1, PM2, PM5, PS3:Supporting
OMIM RCV000015238 SCV000035497 pathogenic Charcot-Marie-Tooth disease type 1B 1996-03-01 no assertion criteria provided literature only

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