ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.199C>T (p.Arg67Cys) (rs775361544)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994158 SCV001147496 uncertain significance not provided 2019-06-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286840 SCV001473459 uncertain significance none provided 2020-04-04 criteria provided, single submitter clinical testing The MPZ c.199C>T; p.Arg67Cys variant (rs775361544) is reported in the literature in two siblings affected with Charcot-Marie-Tooth disease, as well as their asymptomatic mother (Young 2013). However, both affected siblings also carried a PMP22 duplication that was also found in a third affected sibling who did not carry p.Arg67Cys. The p.Arg67Cys variant is found on only seven chromosomes (7/282678 alleles) in the Genome Aggregation Database. The arginine at codon 67 is moderately conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. . Other amino acid substitutions at this codon (p.Arg67His, p.Arg67Pro) have been reported in individuals with symptoms of CMT; however, the clinical significance of these variants in disease is uncertain (Hisama 2005, Antoniadi 2015). Given the lack of clinical and functional data, the significance of the p.Arg67Cys variant is uncertain at this time. References: Antoniadi T et al. Application of targeted multi-gene panel testing for the diagnosis of inherited peripheral neuropathy provides a high diagnostic yield with unexpected phenotype-genotype variability. BMC Med Genet. 2015 Sep 21;16:84. Hisama FM. Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family. Arch Neurol. 2005 Jan;62(1):135-8. Young T et al. Compound Charcot-Marie-Tooth disease: a kindred with severe hereditary neuropathy, pupil abnormalities and a novel MPZ mutation. J Neurol Neurosurg Psychiatry. 2013 Feb;84(2):234-6.
Inherited Neuropathy Consortium RCV000790124 SCV000929515 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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