ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.129_136del (p.Ser44fs)

dbSNP: rs760730366
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235941 SCV000293537 pathogenic not provided 2017-01-09 criteria provided, single submitter clinical testing The c.129_136delCTCCCGGG variant in the MPZ gene has been reported previously as a pathogenic variant associated with CMT; however, no other information was provided (DiVincenzo et al., 2014). The deletion causes a frameshift starting with codon Serine 44, changes this amino acid to an Aspartic acid residue and creates a premature Stop codon at position 10 of the new reading frame, denoted p.Ser44AspfsX10. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This pathogenic variant is predicted to cause loss of normal protein function through protein truncation.
Invitae RCV001390413 SCV001592140 pathogenic Charcot-Marie-Tooth disease, type I 2020-02-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MPZ are known to be pathogenic (PMID: 14711881). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) referred for genetic testing of Charcot-Marie-Tooth disease (PMID: 25614874). ClinVar contains an entry for this variant (Variation ID: 246122). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Ser44Aspfs*10) in the MPZ gene. It is expected to result in an absent or disrupted protein product.
Inherited Neuropathy Consortium RCV000790073 SCV000929463 pathogenic Charcot-Marie-Tooth disease no assertion criteria provided literature only

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