NM_144573.4(NEXN):c.1585_1594del (p.Gln529fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 21, 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:: RCV003022797.2

Allele description [Variation Report for NM_144573.4(NEXN):c.1585_1594del (p.Gln529fs)]

NM_144573.4(NEXN):c.1585_1594del (p.Gln529fs)

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.1585_1594del (p.Gln529fs)

HGVS:

NC_000001.11:g.77942134_77942143del
NG_016625.1:g.58620_58629del
NG_033243.2:g.41959_41968del
NM_001172309.2:c.1393_1402del
NM_144573.4:c.1585_1594delMANE SELECT
NP_001165780.1:p.Gln465fs
NP_653174.3:p.Gln529Leufs
NP_653174.3:p.Gln529fs
LRG_442t1:c.1585_1594del
LRG_442:g.58620_58629del
LRG_442p1:p.Gln529Leufs
LRG_995:g.41959_41968del
NC_000001.10:g.78407811_78407820del
NC_000001.10:g.78407819_78407828del
NM_144573.3:c.1585_1594delCAAAGAAGAA

Protein change:

Q465fs

Molecular consequence:

NM_001172309.2:c.1393_1402del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144573.4:c.1585_1594del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003317125	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003317125

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 21, 2022)

germline

clinical testing

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

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003317125.2

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

Description

This sequence change creates a premature translational stop signal (p.Gln529Leufs*35) in the NEXN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 amino acid(s) of the NEXN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the NEXN protein in which other variant(s) (p.Tyr652Cys) have been observed in individuals with NEXN-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Feb 28, 2024

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