NM_144573.4(NEXN):c.2012T>C (p.Ile671Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 2023
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:: RCV000621846.3

Allele description [Variation Report for NM_144573.4(NEXN):c.2012T>C (p.Ile671Thr)]

NM_144573.4(NEXN):c.2012T>C (p.Ile671Thr)

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.2012T>C (p.Ile671Thr)

HGVS:

NC_000001.11:g.77942813T>C
NG_016625.1:g.59299T>C
NG_033243.2:g.41281A>G
NM_001172309.2:c.1820T>C
NM_144573.4:c.2012T>CMANE SELECT
NP_001165780.1:p.Ile607Thr
NP_653174.3:p.Ile671Thr
NP_653174.3:p.Ile671Thr
LRG_442t1:c.2012T>C
LRG_442:g.59299T>C
LRG_442p1:p.Ile671Thr
LRG_995:g.41281A>G
NC_000001.10:g.78408498T>C
NM_144573.3:c.2012T>C

Protein change:

I607T

Links:

dbSNP: rs747781785

NCBI 1000 Genomes Browser:

rs747781785

Molecular consequence:

NM_001172309.2:c.1820T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_144573.4:c.2012T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000736593	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 14, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30471092, 30847666, 34088380 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000736593

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 14, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.

Richard P, Ader F, Roux M, Donal E, Eicher JC, Aoutil N, Huttin O, Selton-Suty C, Coisne D, Jondeau G, Damy T, Mansencal N, Casalta AC, Michel N, Haentjens J, Faivre L, Lavoute C, Nguyen K, Tregouët DA, Habib G, Charron P.

Clin Genet. 2019 Mar;95(3):356-367. doi: 10.1111/cge.13484. Epub 2018 Dec 27.

PubMed [citation]

PMID:: 30471092

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]

PMID:: 30847666
PMCID:: PMC6533346

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000736593.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.I671T variant (also known as c.2012T>C), located in coding exon 12 of the NEXN gene, results from a T to C substitution at nucleotide position 2012. The isoleucine at codon 671 is replaced by threonine, an amino acid with similar properties. This variant has been detected in individuals from cohorts with dilated cardiomyopathy and noncompaction cardiomyopathy; however, clinical details were limited and variants in other cardiac-related genes were also detected (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309; Richard P et al. Clin Genet, 2019 Mar;95:356-367; Cambon-Viala M et al. J Card Fail, 2021 Jun;27:677-681). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Sep 29, 2024

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