NM_014874.4(MFN2):c.964G>A (p.Glu322Lys) AND Charcot-Marie-Tooth disease type 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 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:: RCV001858778.7

Allele description [Variation Report for NM_014874.4(MFN2):c.964G>A (p.Glu322Lys)]

NM_014874.4(MFN2):c.964G>A (p.Glu322Lys)

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.964G>A (p.Glu322Lys)

HGVS:

NC_000001.11:g.12001548G>A
NG_007945.1:g.26368G>A
NM_001127660.2:c.964G>A
NM_014874.4:c.964G>AMANE SELECT
NP_001121132.1:p.Glu322Lys
NP_055689.1:p.Glu322Lys
LRG_255:g.26368G>A
NC_000001.10:g.12061605G>A
NC_000001.10:g.12061605G>A

Protein change:

E322K

Links:

dbSNP: rs1569852256

NCBI 1000 Genomes Browser:

rs1569852256

Molecular consequence:

NM_001127660.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_014874.4:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

Recent activity

Clear Turn Off Turn On

protein OS-9 isoform 6 precursor [Homo sapiens]
protein OS-9 isoform 6 precursor [Homo sapiens]
gi|387527989|ref|NP_001248350.1|

Protein
protein OS-9 isoform 11 precursor [Homo sapiens]
protein OS-9 isoform 11 precursor [Homo sapiens]
gi|2287780839|ref|NP_001397909.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002157825	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002157825

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV002157825.3

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

Description

This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 806067). This sequence change replaces glutamic acid with lysine at codon 322 of the MFN2 protein (p.Glu322Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine.

#	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 20, 2024

ClinVar

Relating variation to medicine