ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.703_705AAG[1] (p.Lys236del) (rs755446743)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517719 SCV000614115 likely pathogenic not provided 2017-04-13 criteria provided, single submitter clinical testing
GeneDx RCV000517719 SCV000617778 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing The c.706_708delAAG variant in the MPZ gene has been reported previously in families with an autosomal dominant, adult-onset Charcot-Marie-Tooth phenotype; however, additional segregation information was not provided for one family and the c.706_708delAAG variant was identified in two asymptomatic patients in a second family (Street et al., 2002; Sowden et al., 2005). The c.706_708delAAG variant results in an in-frame deletion of one amino acid residue, denoted p.Lys236del. The deleted residue occurs at a position that is conserved across species. The c.706_708delAAG variant is observed in 7/125140 (0.01%) alleles from individuals of non-Finnish European background in large population databases (Lek et al., 2016). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000819196 SCV000959843 pathogenic Charcot-Marie-Tooth disease, type I 2020-01-14 criteria provided, single submitter clinical testing This variant, c.706_708delAAG, results in the deletion of 1 amino acid(s) of the MPZ protein (p.Lys236del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755446743, ExAC 0.002%). This variant has been observed to segregate with late-onset Charcot-Marie-Tooth disease in families (PMID: 12207932, 15716547). ClinVar contains an entry for this variant (Variation ID: 447734). This variant has been reported to affect MPZ protein function (PMID: 29687021, 31173589). This variant is also known as K263Del in the literature. For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,London Health Sciences Centre RCV000789487 SCV001336809 likely pathogenic Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789487 SCV000928843 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
GenomeConnect, ClinGen RCV000845000 SCV000986830 not provided Charcot-Marie-Tooth disease type 2J; Charcot-Marie-Tooth disease, demyelinating, type 1b; Dejerine-Sottas disease; Congenital hypomyelinating neuropathy no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 07/27/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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