ClinVar Miner

Submissions for variant NM_000530.8(MPZ):c.389A>G (p.Lys130Arg) (rs281865127)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000516461 SCV000228899 uncertain significance not provided 2015-04-02 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000516461 SCV000614108 pathogenic not provided 2017-01-31 criteria provided, single submitter clinical testing
Invitae RCV000819474 SCV000960137 pathogenic Charcot-Marie-Tooth disease, type I 2018-12-14 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 130 of the MPZ protein (p.Lys130Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with Charcot-Marie-Tooth disease type 1B in a family (PMID: 8938258) and has been reported in several additional affected individuals (PMID: 29670817, 26454100, 10923043, 27353517). This variant has also been observed to be de novo in individuals affected with Dejerine-Sottas syndrome (PMID: 12090401). ClinVar contains an entry for this variant (Variation ID: 41021). Experimental studies have shown that this missense change leads to reduced expression of the MPZ protein in patient nerve biopsies (PMID: 11182278). 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. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000033918 SCV001135456 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2019-05-28 criteria provided, single submitter clinical testing
GeneReviews RCV000033918 SCV000057835 pathogenic Charcot-Marie-Tooth disease, demyelinating, type 1b 2015-03-26 no assertion criteria provided literature only

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