NM_144573.4(NEXN):c.643C>G (p.Gln215Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 28, 2018
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:: RCV000690402.1

Allele description [Variation Report for NM_144573.4(NEXN):c.643C>G (p.Gln215Glu)]

NM_144573.4(NEXN):c.643C>G (p.Gln215Glu)

Gene:

NEXN:nexilin F-actin binding protein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_144573.4(NEXN):c.643C>G (p.Gln215Glu)

HGVS:

NC_000001.11:g.77926567C>G
NG_016625.1:g.43053C>G
NM_001172309.2:c.451C>G
NM_144573.4:c.643C>GMANE SELECT
NP_001165780.1:p.Gln151Glu
NP_653174.3:p.Gln215Glu
NP_653174.3:p.Gln215Glu
LRG_442t1:c.643C>G
LRG_442:g.43053C>G
LRG_442p1:p.Gln215Glu
NC_000001.10:g.78392252C>G
NM_144573.3:c.643C>G

Protein change:

Q151E

Links:

dbSNP: rs1557981819

NCBI 1000 Genomes Browser:

rs1557981819

Molecular consequence:

NM_001172309.2:c.451C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_144573.4:c.643C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1CC (CMD1CC)
Identifiers:: MONDO: MONDO:0013147; MedGen: C2751084; Orphanet: 154; OMIM: 613122

Name:: Hypertrophic cardiomyopathy 20
Synonyms:: Familial hypertrophic cardiomyopathy 20
Identifiers:: MONDO: MONDO:0013477; MedGen: C3151267; OMIM: 613876

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000818086	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 28, 2018)	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

SCV000818086

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 28, 2018)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000818086.1

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

Description

This sequence change replaces glutamine with glutamic acid at codon 215 of the NEXN protein (p.Gln215Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NEXN-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

#	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: Apr 6, 2024

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