ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.293G>A (p.Arg98His) (rs121913589)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196172 SCV000253842 pathogenic Charcot-Marie-Tooth disease, type I 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 98 of the MPZ protein (p.Arg98His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease type 1 (CMT1) in a single family (PMID: 7688964). This variant has also been reported in several unrelated CMT1 patients (PMID: 8644725, 20215982, 10581375, 12477701). ClinVar contains an entry for this variant (Variation ID: 14176). Experimental studies have shown that this variant causes cellular mislocalization of the MPZ protein (PMID: 20461396). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000376287 SCV000329714 pathogenic not provided 2021-04-30 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31372974, 33179255, 31211173, 29687021, 11437164, 10581375, 20215982, 8644725, 10737979, 7688964, 8797476, 12221176, 20461396)
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415463 SCV000492978 likely pathogenic Decreased nerve conduction velocity; Sensory neuropathy; Pes cavus; Distal muscle weakness; Distal lower limb amyotrophy 2014-09-19 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000376287 SCV000614105 pathogenic not provided 2015-03-12 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality. Found in multiple individuals with expected phenotype for this gene. This variant occurs as the most likely explanation for disease in a significant number of internal cases, suggesting this variant is associated with disease. Assessment of experimental evidence suggests this variant results in abnormal protein function. Segregates with disease in multiple families
CeGaT Praxis fuer Humangenetik Tuebingen RCV000376287 SCV001249786 pathogenic not provided 2018-03-01 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001173692 SCV001336802 pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000376287 SCV001713094 pathogenic not provided 2019-10-06 criteria provided, single submitter clinical testing
OMIM RCV000015239 SCV000035498 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2002-09-10 no assertion criteria provided literature only

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