NM_014874.4(MFN2):c.707C>T (p.Thr236Met) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 1, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001257085.17

Allele description

NM_014874.4(MFN2):c.707C>T (p.Thr236Met)

Gene:

MFN2:mitofusin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_014874.4(MFN2):c.707C>T (p.Thr236Met)

HGVS:

NC_000001.11:g.11998877C>T
NG_007945.1:g.23697C>T
NM_001127660.2:c.707C>T
NM_014874.4:c.707C>TMANE SELECT
NP_001121132.1:p.Thr236Met
NP_001121132.1:p.Thr236Met
NP_055689.1:p.Thr236Met
NP_055689.1:p.Thr236Met
LRG_255t1:c.707C>T
LRG_255:g.23697C>T
LRG_255p1:p.Thr236Met
NC_000001.10:g.12058934C>T
NM_001127660.1:c.707C>T
NM_014874.3:c.707C>T

Protein change:

T236M

Links:

dbSNP: rs773159585

NCBI 1000 Genomes Browser:

rs773159585

Molecular consequence:

NM_001127660.2:c.707C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.707C>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
SCV001364385	Department of Paediatrics and Adolescent Medicine, The University of Hong Kong	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 2, 2020)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 32963807
SCV001783928	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 25, 2020)	germline	clinical testing	Citation Link,
SCV002585025	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Sep 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001364385

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 2, 2020)

unknown

research

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

SCV001783928

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 25, 2020)

germline

clinical testing

Citation Link,

SCV002585025

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Sep 1, 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	unknown	unknown	not provided	not provided	not provided	not provided	no	research
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A three-year follow-up study evaluating clinical utility of exome sequencing and diagnostic potential of reanalysis.

Fung JLF, Yu MHC, Huang S, Chung CCY, Chan MCY, Pajusalu S, Mak CCY, Hui VCC, Tsang MHY, Yeung KS, Lek M, Chung BHY.

NPJ Genom Med. 2020;5(1):37. doi: 10.1038/s41525-020-00144-x.

PubMed [citation]

PMID:: 32963807
PMCID:: PMC7484757

Details of each submission

From Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, SCV001364385.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	no	research	PubMed (2)

Description

By the ACMG guideline 2015, this variant is classified as likely pathogenic (PM1, PM2, PP2, PP3) with multiple affected individuals reported. Our patient does not habour typical features of Charcot Marie Tooth disease or neuropathy. Rather, he presented with other neurological issues such as intellectual disability, behavioural problems and seizure.

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

From GeneDx, SCV001783928.1

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

Description

Reported as heterozygous in an individual with Charcot-Marie-Tooth disease who was also heterozygous for a de novo variant in the GDAP1 gene; the variant in MFN2 was also present in the asymptomatic mother and the maternal grandfather with adult onset neuropathy (Kostera-Pruszczyk et al., 2014); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32963807, 15549395, 25403865, 30373780, 30340945)

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV002585025.11

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

Description

MFN2: PM1, PM2, 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		1	not provided	not provided	not provided

Last Updated: Jun 17, 2024

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