ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.200G>A (p.Arg67His) (rs201720099)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228125 SCV000285036 uncertain significance Charcot-Marie-Tooth disease, type I 2019-11-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 67 of the MPZ protein (p.Arg67His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201720099, ExAC 0.002%). This variant has been reported in an individual affected with CMT1 (PMID: 26392352). Familial segregation studies were not performed and the clinical significance of this variant was not determined. This variant has also been reported in two siblings with clinical features of CMT1 and CMT2. However, these siblings carried a pathogenic mutation in a different gene consistent with CMT1 (PMID: 23197742). In addition, this variant has been observed in a reportedly unaffected individual at Invitae (Invitae database). ClinVar contains an entry for this variant (Variation ID: 237875). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000479710 SCV000565178 likely benign not specified 2018-01-17 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV001097629 SCV001253926 uncertain significance Congenital hypomyelinating neuropathy 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001097630 SCV001253927 uncertain significance Charcot-Marie-Tooth disease, demyelinating, type 1b 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001097631 SCV001253928 uncertain significance Charcot-Marie-Tooth disease dominant intermediate d 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001097632 SCV001253929 uncertain significance Roussy-Lévy syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001174319 SCV001337452 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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