NM_000530.8(MPZ):c.638_639del (p.Gly213fs) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 8, 2020
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:: RCV001390456.7

Allele description [Variation Report for NM_000530.8(MPZ):c.638_639del (p.Gly213fs)]

NM_000530.8(MPZ):c.638_639del (p.Gly213fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.638_639del (p.Gly213fs)

HGVS:

NC_000001.11:g.161306115_161306116del
NG_008055.1:g.8858_8859del
NM_000530.8:c.638_639delMANE SELECT
NM_001315491.2:c.638_639del
NP_000521.2:p.Gly213fs
NP_001302420.1:p.Gly213fs
LRG_256:g.8858_8859del
NC_000001.10:g.161275904_161275905del
NC_000001.10:g.161275905_161275906del

Protein change:

G213fs

Links:

dbSNP: rs2102257572

NCBI 1000 Genomes Browser:

rs2102257572

Molecular consequence:

NM_000530.8:c.638_639del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001315491.2:c.638_639del - 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
SCV001592196	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7530550, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001592196

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2020)

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

Identification of a de novo insertional mutation in P0 in a patient with a Déjérine-Sottas syndrome (DSS) phenotype.

Rautenstrauss B, Nelis E, Grehl H, Pfeiffer RA, Van Broeckhoven C.

Hum Mol Genet. 1994 Sep;3(9):1701-2. No abstract available.

PubMed [citation]

PMID:: 7530550

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, SCV001592196.5

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

Description

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 results in a premature translational stop signal in the MPZ gene (p.Gly213Alafs*21). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acids of the MPZ protein. This variant disrupts the C-terminus of the MPZ protein. Other variant(s) that disrupt this region (p.Glu222Valfs*14) have been determined to be pathogenic (PMID: 7530550). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#	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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