NM_001308093.3(GATA4):c.1318A>G (p.Ile440Val) AND Atrioventricular septal defect 4

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 18, 2020
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:: RCV001347518.6

Allele description

NM_001308093.3(GATA4):c.1318A>G (p.Ile440Val)

Gene:

GATA4:GATA binding protein 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p23.1

Genomic location:

Preferred name:

NM_001308093.3(GATA4):c.1318A>G (p.Ile440Val)

HGVS:

NC_000008.11:g.11758461A>G
NG_008177.2:g.86543A>G
NM_001308093.3:c.1318A>GMANE SELECT
NM_001308094.2:c.697A>G
NM_001374273.1:c.697A>G
NM_001374274.1:c.571A>G
NM_002052.5:c.1315A>G
NP_001295022.1:p.Ile440Val
NP_001295023.1:p.Ile233Val
NP_001361202.1:p.Ile233Val
NP_001361203.1:p.Ile191Val
NP_002043.2:p.Ile439Val
NC_000008.10:g.11615970A>G

Protein change:

I191V

Links:

dbSNP: rs772619099

NCBI 1000 Genomes Browser:

rs772619099

Molecular consequence:

NM_001308093.3:c.1318A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.697A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.697A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374274.1:c.571A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.1315A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Atrioventricular septal defect 4 (AVSD4)
Identifiers:: MONDO: MONDO:0013747; MedGen: C3280781; OMIM: 614430

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001541784	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 18, 2020)	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

SCV001541784

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 18, 2020)

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 Invitae, SCV001541784.4

#	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 replaces isoleucine with valine at codon 439 of the GATA4 protein (p.Ile439Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs772619099, ExAC 0.01%). This variant has not been reported in the literature in individuals with GATA4-related conditions. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: Mar 5, 2024

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