NM_144573.4(NEXN):c.1609_1610insA (p.Leu537fs) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Jul 28, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000301273.3

Allele description [Variation Report for NM_144573.4(NEXN):c.1609_1610insA (p.Leu537fs)]

NM_144573.4(NEXN):c.1609_1610insA (p.Leu537fs)

Gene:
NEXN:nexilin F-actin binding protein [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
1p31.1
Genomic location:
Preferred name:
NM_144573.4(NEXN):c.1609_1610insA (p.Leu537fs)
HGVS:
  • NC_000001.11:g.77942158_77942159insA
  • NG_016625.1:g.58644_58645insA
  • NG_033243.2:g.41935_41936insT
  • NM_001172309.2:c.1417_1418insA
  • NM_144573.4:c.1609_1610insAMANE SELECT
  • NP_001165780.1:p.Leu473fs
  • NP_653174.3:p.Leu537fs
  • NP_653174.3:p.Leu537fs
  • LRG_442t1:c.1609_1610insA
  • LRG_442:g.58644_58645insA
  • LRG_442p1:p.Leu537fs
  • LRG_995:g.41935_41936insT
  • NC_000001.10:g.78407843_78407844insA
  • NM_144573.3:c.1609_1610insA
  • p.Leu537TyrfsX7
Protein change:
L473fs
Links:
dbSNP: rs779350415
NCBI 1000 Genomes Browser:
rs779350415
Molecular consequence:
  • NM_001172309.2:c.1417_1418insA - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_144573.4:c.1609_1610insA - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000712380Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jul 28, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000712380.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Leu537fs variant in NEXN has not been previously reported in individuals with cardiomyopa thy, but has been identified in 1/66208 European chromosomes by the Exome Aggreg ation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs779350415). This variant is predicted to cause a frameshift, which alters the protein?s amino ac id sequence beginning at position 537 and leads to a premature termination codon 7 amino acids downstream. Although the severe nature of this change increases t he likelihood that the variant is pathogenic, the NEXN gene has not been widely studied and the spectrum of variants leading to disease is not well-defined. Los s of NEXN function has been shown to cause DCM in zebrafish; however, it remains unclear if one or both copies of the gene need to be affected to cause disease (Hassel 2009, Wang 2010). In summary, while there is some suspicion for a pathog enic role, the clinical significance of the p.Leu537fs variant is uncertain.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Dec 4, 2021

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