ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.371C>T (p.Thr124Met) (rs121913595)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517355 SCV000614106 pathogenic not provided 2020-10-09 criteria provided, single submitter clinical testing This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families. This variant occurs as the most likely explanation for disease in a significant number of internal cases, suggesting this variant is associated with disease. Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure.
Invitae RCV000638155 SCV000759641 pathogenic Charcot-Marie-Tooth disease, type I 2020-05-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 124 of the MPZ protein (p.Thr124Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease in multiple families (PMID: 12948789, 15159512, 19629567, 25720167) and has also been reported in several unrelated affected individuals (PMID: 9452091, 26234237, 12207153, 10923043, 16279991). ClinVar contains an entry for this variant (Variation ID: 14181). Experimental studies have shown that this missense change decreases myelin protein zero mediated intracellular adhesion (PMID: 20461396, 18337304). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763262 SCV000893900 pathogenic Charcot-Marie-Tooth disease type 2I; Charcot-Marie-Tooth disease type 2J; Charcot-Marie-Tooth disease, demyelinating, type 1b; Charcot-Marie-Tooth disease dominant intermediate d; Roussy-Lévy syndrome; Dejerine-Sottas disease; Congenital hypomyelinating neuropathy 1, autosomal recessive 2018-10-31 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000517355 SCV001249783 pathogenic not provided 2017-10-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262744 SCV001440723 pathogenic Charcot-Marie-Tooth disease dominant intermediate d 2019-01-01 criteria provided, single submitter clinical testing
OMIM RCV000015244 SCV000035503 pathogenic Charcot-Marie-Tooth disease type 2J 2006-06-15 no assertion criteria provided literature only
OMIM RCV000015245 SCV000035504 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2006-06-15 no assertion criteria provided literature only
GeneReviews RCV000015245 SCV000057834 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000192248 SCV000929509 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Genomics England Pilot Project,Genomics England RCV001262744 SCV001759992 likely pathogenic Charcot-Marie-Tooth disease dominant intermediate d no assertion criteria provided clinical testing

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