ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.103G>A (p.Asp35Asn) (rs121913596)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558954 SCV000636237 pathogenic Charcot-Marie-Tooth disease, type I 2017-07-31 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 35 of the MPZ protein (p.Asp35Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot MarieTooth disease (CMT) in a single family (PMID: 24444136) and has been reported in several individuals with CMT (PMID: 20385006, 24053775, 23106488). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different variant (c.103G>T) giving rise to (p.Asp35ty) has been reported in a family affected with CMT (PMID: 10406984), indicating that this residue may be critical for protein function. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000995582 SCV001149841 pathogenic Charcot-Marie-Tooth disease type 2I 2019-10-09 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001093015 SCV001249790 pathogenic not provided 2020-01-01 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000790058 SCV000929448 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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