NM_000530.8(MPZ):c.361G>A (p.Asp121Asn) AND Charcot-Marie-Tooth disease, type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 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:: RCV001856276.7

Allele description [Variation Report for NM_000530.8(MPZ):c.361G>A (p.Asp121Asn)]

NM_000530.8(MPZ):c.361G>A (p.Asp121Asn)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.361G>A (p.Asp121Asn)

HGVS:

NC_000001.11:g.161306795C>T
NG_008055.1:g.8178G>A
NM_000530.8:c.361G>AMANE SELECT
NM_001315491.2:c.361G>A
NP_000521.2:p.Asp121Asn
NP_001302420.1:p.Asp121Asn
LRG_256:g.8178G>A
NC_000001.10:g.161276585C>T
NC_000001.10:g.161276585C>T

Protein change:

D121N

Links:

dbSNP: rs1670263519

NCBI 1000 Genomes Browser:

rs1670263519

Molecular consequence:

NM_000530.8:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.361G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002229888	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27774063, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002229888

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 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

A Novel Asp121Asn Mutation of Myelin Protein Zero Is Associated with Late-Onset Axonal Charcot-Marie-Tooth Disease, Hearing Loss and Pupil Abnormalities.

Duan X, Gu W, Hao Y, Wang R, Wen H, Sun S, Jiao J, Fan D.

Front Aging Neurosci. 2016;8:222.

PubMed [citation]

PMID:: 27774063
PMCID:: PMC5054897

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002229888.3

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 27774063). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 872512). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with asparagine at codon 121 of the MPZ protein (p.Asp121Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine.

#	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: Oct 8, 2024

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