NM_144573.4(NEXN):c.1366G>A (p.Gly456Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 19, 2021
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:: RCV001215702.8

Allele description [Variation Report for NM_144573.4(NEXN):c.1366G>A (p.Gly456Arg)]

NM_144573.4(NEXN):c.1366G>A (p.Gly456Arg)

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.1366G>A (p.Gly456Arg)

HGVS:

NC_000001.11:g.77935937G>A
NG_016625.1:g.52423G>A
NM_001172309.2:c.1174G>A
NM_144573.4:c.1366G>AMANE SELECT
NP_001165780.1:p.Gly392Arg
NP_653174.3:p.Gly456Arg
NP_653174.3:p.Gly456Arg
LRG_442t1:c.1366G>A
LRG_442:g.52423G>A
LRG_442p1:p.Gly456Arg
NC_000001.10:g.78401622G>A
NM_144573.3:c.1366G>A
c.1366G>A

Protein change:

G392R

Links:

dbSNP: rs397517844

NCBI 1000 Genomes Browser:

rs397517844

Molecular consequence:

NM_001172309.2:c.1174G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_144573.4:c.1366G>A - 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

Recent activity

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Homo sapiens acyl-Coenzyme A binding domain containing 3, mRNA (cDNA clone MGC:71593 IMAGE:4813993), complete cds
gi|38511511|gb|BC060792.1|

Nucleotide
Profile neighbors for GEO Profiles (Select 129258666) (200)
GEO Profiles
Related DataSets for GEO Profiles (Select 129240147) (1)
GEO DataSets
In vitro myoblast differentiation: time course
In vitro myoblast differentiation: time course
Accession: GDS5632

GEO DataSets
JGI_CAAR4679.rev NIH_XGC_tropLiv1 Xenopus tropicalis cDNA clone IMAGE:7737403 3'...
JGI_CAAR4679.rev NIH_XGC_tropLiv1 Xenopus tropicalis cDNA clone IMAGE:7737403 3', mRNA sequence
gi|59206394|gnl|dbEST|27738705|gb|D 74.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001387461	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 19, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001387461

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 19, 2021)

germline

clinical testing

PubMed (2)
[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

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

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, SCV001387461.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is present in population databases (rs397517844, ExAC 0.01%). This sequence change replaces glycine with arginine at codon 456 of the NEXN protein (p.Gly456Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 47888). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0").

#	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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