NM_181703.4(GJA5):c.695del (p.Lys232fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 20, 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:: RCV003805708.2

Allele description [Variation Report for NM_181703.4(GJA5):c.695del (p.Lys232fs)]

NM_181703.4(GJA5):c.695del (p.Lys232fs)

Genes:

LOC122128420:Sharpr-MPRA regulatory region 3144 [Gene]
GJA5:gap junction protein alpha 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q21.2

Genomic location:

Preferred name:

NM_181703.4(GJA5):c.695del (p.Lys232fs)

HGVS:

NC_000001.11:g.147758545del
NG_009369.2:g.19831del
NG_076440.1:g.265del
NM_005266.7:c.695del
NM_181703.4:c.695delMANE SELECT
NP_005257.2:p.Lys232fs
NP_859054.1:p.Lys232fs
NC_000001.10:g.147230652del
NC_000001.10:g.147230653del

Protein change:

K232fs

Molecular consequence:

NM_005266.7:c.695del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_181703.4:c.695del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Atrial standstill 1 (ATRST1)
Synonyms:: ATRIAL CARDIOMYOPATHY WITH HEART BLOCK; CARDIOMYOPATHY, FAMILIAL, WITH CONDUCTION DISTURBANCE; Atrial standstill, digenic (GJA5/SCN5A)
Identifiers:: MONDO: MONDO:0007171; MedGen: C4551959; Orphanet: 1344; OMIM: 108770

Name:: Atrial fibrillation, familial, 11 (ATFB11)
Identifiers:: MONDO: MONDO:0013544; MedGen: C3279693; OMIM: 614049

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004588969	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 20, 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

SCV004588969

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 20, 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004588969.1

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

Description

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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with GJA5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys232Argfs*26) in the GJA5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 127 amino acid(s) of the GJA5 protein.

#	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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