NM_000530.8(MPZ):c.424del (p.Val142fs) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 22, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001929065.3

Allele description [Variation Report for NM_000530.8(MPZ):c.424del (p.Val142fs)]

NM_000530.8(MPZ):c.424del (p.Val142fs)

Gene:

MPZ:myelin protein zero [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.424del (p.Val142fs)

HGVS:

NC_000001.11:g.161306733del
NG_008055.1:g.8241del
NM_000530.8:c.424delMANE SELECT
NM_001315491.2:c.424del
NP_000521.2:p.Val142fs
NP_001302420.1:p.Val142fs
LRG_256:g.8241del
NC_000001.10:g.161276522del
NC_000001.10:g.161276523del

Protein change:

V142fs

Links:

dbSNP: rs2102258700

NCBI 1000 Genomes Browser:

rs2102258700

Molecular consequence:

NM_000530.8:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001315491.2:c.424del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Charcot-Marie-Tooth disease, type I (CMT1)
Synonyms:: Charcot-Marie-Tooth Neuropathy Type 1; Hereditary Motor and Sensory Neuropathy 1; Charcot-Marie-Tooth, Type 1
Identifiers:: MONDO: MONDO:0019011; MedGen: C0751036

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002198436	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 22, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14711881, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002198436

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 22, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotypic clustering in MPZ mutations.

Shy ME, Jáni A, Krajewski K, Grandis M, Lewis RA, Li J, Shy RR, Balsamo J, Lilien J, Garbern JY, Kamholz J.

Brain. 2004 Feb;127(Pt 2):371-84. Epub 2004 Jan 7. Review.

PubMed [citation]

PMID:: 14711881

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002198436.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with MPZ-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val142Serfs*20) in the MPZ gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPZ are known to be pathogenic (PMID: 14711881).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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