VCV000637508.5 - ClinVar

NM_000530.8(MPZ):c.204C>A (p.Tyr68Ter)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (1)

1 out of 2 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000530.8(MPZ):c.204C>A (p.Tyr68Ter)

Variation ID: 637508 Accession: VCV000637508.5

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q23.3 1: 161307288 (GRCh38) [ NCBI UCSC ] 1: 161277078 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 27, 2019	Feb 15, 2026	Nov 28, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000530.8:c.204C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000521.2:p.Tyr68Ter	nonsense
NM_001315491.2:c.204C>A	NP_001302420.1:p.Tyr68Ter	nonsense
NC_000001.11:g.161307288G>T
NC_000001.10:g.161277078G>T
NG_008055.1:g.7685C>A
LRG_256:g.7685C>A
LRG_256t1:c.204C>A

... more HGVS ... less HGVS

Protein change

Y68*

Other names

Canonical SPDI

NC_000001.11:161307287:G:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA343350514 dbSNP: rs1571819906 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MPZ		-	-	GRCh38 GRCh37	729	766

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Charcot-Marie-Tooth disease	Pathogenic (1)	no assertion criteria provided	-	RCV000789716.1
Charcot-Marie-Tooth disease, type I	Pathogenic (1)	criteria provided, single submitter	Nov 28, 2023	RCV002536919.5

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Nov 28, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Charcot-Marie-Tooth disease, type I	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003523260.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 15, 2026	Publications: PubMed (1) PubMed: 14711881 Comment: show This sequence change creates a premature translational stop signal (p.Tyr68*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 637508). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (-) N Not contributing to aggregate classification	no assertion criteria provided	Charcot-Marie-Tooth disease	Inherited Neuropathy Consortium Accession: SCV000929092.1 First in ClinVar: Jul 27, 2019 Last updated: Jul 27, 2019	Publications: PubMed (1) PubMed: 25614874 Observation: 1 Collection method: literature only Allele origin: germline Affected status: yes Observation 1 Collection method: literature only Allele origin: germline Affected status: yes

Comment:

This sequence change creates a premature translational stop signal (p.Tyr68*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MPZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 637508). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The allelic spectrum of Charcot-Marie-Tooth disease in over 17,000 individuals with neuropathy.	DiVincenzo C	Molecular genetics & genomic medicine	2014	PMID: 25614874
Phenotypic clustering in MPZ mutations.	Shy ME	Brain : a journal of neurology	2004	PMID: 14711881

Text-mined citations for rs1571819906 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026