NM_000530.8(MPZ):c.371C>T (p.Thr124Met) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jul 1, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000517355.35

Allele description [Variation Report for NM_000530.8(MPZ):c.371C>T (p.Thr124Met)]

NM_000530.8(MPZ):c.371C>T (p.Thr124Met)

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.371C>T (p.Thr124Met)

HGVS:

NC_000001.11:g.161306785G>A
NG_008055.1:g.8188C>T
NM_000530.8:c.371C>TMANE SELECT
NM_001315491.2:c.371C>T
NP_000521.2:p.Thr124Met
NP_000521.2:p.Thr124Met
NP_001302420.1:p.Thr124Met
LRG_256t1:c.371C>T
LRG_256:g.8188C>T
LRG_256p1:p.Thr124Met
NC_000001.10:g.161276575G>A
NM_000530.5:c.401C>T
NM_000530.6:c.371C>T
NM_000530.7:c.371C>T
NP_000521.1:p.Thr134Met
P25189:p.Thr124Met

Protein change:

T124M; THR124MET

Links:

UniProtKB: P25189#VAR_004529; OMIM: 159440.0016; dbSNP: rs121913595

NCBI 1000 Genomes Browser:

rs121913595

Molecular consequence:

NM_000530.8:c.371C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.371C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000614106	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Pathogenic (Oct 9, 2020)	unknown	clinical testing	PubMed (13) [See all records that cite these PMIDs] 12911457, 19629567, 26234237, 25720167, 15377707, 12948789, 20461396, 10071056, 12207153, 15159512, 11080237, 9452091, 26467025
SCV001249783	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2022)	germline	clinical testing	Citation Link,
SCV002520050	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 19, 2021)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 10835936, 16279991, 18337304, 19629567, 19928689, 20461396, 25720167, 26234237, 31211173, 31827005, 25741868
SCV002540333	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 29, 2022)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Axonal and demyelinating forms of the MPZ Thr124Met mutation.

Kurihara S, Adachi Y, Wada K, Adachi A, Ohama E, Nakashima K.

Acta Neurol Scand. 2003 Sep;108(3):157-60.

PubMed [citation]

PMID:: 12911457

Charcot-Marie-Tooth families in Japan with MPZ Thr124Met mutation.

Kurihara S, Adachi Y, Imai C, Araki H, Hattori N, Numakura C, Lin Y, Hayasaka K, Sobue G, Nakashima K.

J Neurol Neurosurg Psychiatry. 2004 Oct;75(10):1492-4.

PubMed [citation]

PMID:: 15377707
PMCID:: PMC1738775

See all PubMed Citations (20)

Details of each submission

From Athena Diagnostics, SCV000614106.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

This variant was not reported in large, multi-ethnic, general populations (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families. This variant occurs as the most likely explanation for disease in a significant number of internal cases, suggesting this variant is associated with disease. Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure.

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

From CeGaT Center for Human Genetics Tuebingen, SCV001249783.26

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

Description

MPZ: PM1, PM2, PP1:Moderate, PS3:Moderate, PS4:Moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV002520050.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

PP1, PM1, PM2, PS3_moderate, PS4

#	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

From GeneDx, SCV002540333.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in multiple unrelated patients with Charcot-Marie-Tooth (Yoshihara et al., 2000; Gallardo et al., 2009; Liu et al., 2013; Bergamin et al., 2014); Published functional studies demonstrate a damaging effect (Grandis et al., 2008; Lee et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (HGMD); This variant is associated with the following publications: (PMID: 15159512, 19928689, 24819634, 18563718, 18337304, 20461396, 19629567, 10835936, 9452091, 25720167, 26234237, 16279991, 24028194, 15377707, 10071056, 34210210, 33825325, 22820753, 20301384, 16775239, 12911457, 31827005, 30018047, 29516875, 10329755, 25802885, 29687021, 31211173, 12948789, 12207153, 10764043, 26310628, 10923043)

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

Last Updated: Oct 26, 2024

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