NM_144573.4(NEXN):c.1955A>G (p.Tyr652Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 1, 2022
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:: RCV000234084.7

Allele description [Variation Report for NM_144573.4(NEXN):c.1955A>G (p.Tyr652Cys)]

NM_144573.4(NEXN):c.1955A>G (p.Tyr652Cys)

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.1955A>G (p.Tyr652Cys)

Other names:

p.Y652C:TAT>TGT

HGVS:

NC_000001.11:g.77942756A>G
NG_016625.1:g.59242A>G
NG_033243.2:g.41338T>C
NM_001172309.2:c.1763A>G
NM_144573.4:c.1955A>GMANE SELECT
NP_001165780.1:p.Tyr588Cys
NP_653174.3:p.Tyr652Cys
NP_653174.3:p.Tyr652Cys
LRG_442t1:c.1955A>G
LRG_442:g.59242A>G
LRG_442p1:p.Tyr652Cys
LRG_995:g.41338T>C
NC_000001.10:g.78408441A>G
NM_144573.3:c.1955A>G
Q0ZGT2:p.Tyr652Cys
c.1955A>G

Protein change:

Y588C; TYR652CYS

Links:

UniProtKB: Q0ZGT2#VAR_063011; OMIM: 613121.0002; dbSNP: rs137853197

NCBI 1000 Genomes Browser:

rs137853197

Molecular consequence:

NM_001172309.2:c.1763A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_144573.4:c.1955A>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
SCV000291369	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 1, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24503780, 29253866, 30847666, 19881492, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000291369

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 1, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

High proportion of genetic cases in patients with advanced cardiomyopathy including a novel homozygous Plakophilin 2-gene mutation.

Klauke B, Gaertner-Rommel A, Schulz U, Kassner A, Zu Knyphausen E, Laser T, Kececioglu D, Paluszkiewicz L, Blanz U, Sandica E, van den Bogaerdt AJ, van Tintelen JP, Gummert J, Milting H.

PLoS One. 2017;12(12):e0189489. doi: 10.1371/journal.pone.0189489.

PubMed [citation]

PMID:: 29253866
PMCID:: PMC5734774

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000291369.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 652 of the NEXN protein (p.Tyr652Cys). This variant is present in population databases (rs137853197, gnomAD 0.01%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 19881492, 24503780, 29253866, 30847666). ClinVar contains an entry for this variant (Variation ID: 326). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects NEXN function (PMID: 19881492). 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: Nov 3, 2024

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