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NM_144573.4(NEXN):c.166_169del (p.Arg56fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 5, 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:
RCV002536604.2

Allele description [Variation Report for NM_144573.4(NEXN):c.166_169del (p.Arg56fs)]

NM_144573.4(NEXN):c.166_169del (p.Arg56fs)

Gene:
NEXN:nexilin F-actin binding protein [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1p31.1
Genomic location:
Preferred name:
NM_144573.4(NEXN):c.166_169del (p.Arg56fs)
HGVS:
  • NC_000001.11:g.77917704_77917707del
  • NG_016625.1:g.34190_34193del
  • NM_001172309.2:c.28-256_28-253del
  • NM_144573.4:c.166_169delMANE SELECT
  • NP_653174.3:p.Arg56fs
  • NP_653174.3:p.Arg56fs
  • LRG_442t1:c.166_169del
  • LRG_442:g.34190_34193del
  • LRG_442p1:p.Arg56fs
  • NC_000001.10:g.78383387_78383390del
  • NC_000001.10:g.78383389_78383392del
  • NM_144573.3:c.166_169del
Protein change:
R56fs
Links:
dbSNP: rs765396527
NCBI 1000 Genomes Browser:
rs765396527
Molecular consequence:
  • NM_144573.4:c.166_169del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001172309.2:c.28-256_28-253del - intron variant - [Sequence Ontology: SO:0001627]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003511658Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 5, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Next-generation sequencing in prenatal setting: Some examples of unexpected variant association.

Rinaldi B, Race V, Corveleyn A, Van Hoof E, Bauters M, Van Den Bogaert K, Denayer E, de Ravel T, Legius E, Baldewijns M, Aertsen M, Lewi L, De Catte L, Breckpot J, Devriendt K.

Eur J Med Genet. 2020 May;63(5):103875. doi: 10.1016/j.ejmg.2020.103875. Epub 2020 Feb 10.

PubMed [citation]
PMID:
32058062

Homozygous G650del nexilin variant causes cardiomyopathy in mice.

Liu C, Spinozzi S, Feng W, Chen Z, Zhang L, Zhu S, Wu T, Fang X, Ouyang K, Evans SM, Chen J.

JCI Insight. 2020 Aug 20;5(16). doi:pii: 138780. 10.1172/jci.insight.138780.

PubMed [citation]
PMID:
32814711
PMCID:
PMC7455123
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003511658.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 626385). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. This variant is present in population databases (rs765396527, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Arg56Glufs*34) in the NEXN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEXN are known to be pathogenic (PMID: 32058062, 32814711, 32870709, 33949776).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024