NM_001308093.3(GATA4):c.931A>C (p.Met311Leu) AND Atrioventricular septal defect 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 24, 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:: RCV001369186.6

Allele description [Variation Report for NM_001308093.3(GATA4):c.931A>C (p.Met311Leu)]

NM_001308093.3(GATA4):c.931A>C (p.Met311Leu)

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.931A>C (p.Met311Leu)

HGVS:

NC_000008.11:g.11755064A>C
NG_008177.2:g.83146A>C
NM_001308093.3:c.931A>CMANE SELECT
NM_001308094.2:c.310A>C
NM_001374273.1:c.310A>C
NM_001374274.1:c.184A>C
NM_002052.5:c.928A>C
NP_001295022.1:p.Met311Leu
NP_001295023.1:p.Met104Leu
NP_001361202.1:p.Met104Leu
NP_001361203.1:p.Met62Leu
NP_002043.2:p.Met310Leu
NC_000008.10:g.11612573A>C

Protein change:

M104L

Links:

dbSNP: rs387906772

NCBI 1000 Genomes Browser:

rs387906772

Molecular consequence:

NM_001308093.3:c.931A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.310A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.310A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374274.1:c.184A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.928A>C - 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
SCV001565616	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 24, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20347099, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001565616

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 24, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

A novel mutation in GATA4 gene associated with dominant inherited familial atrial septal defect.

Chen Y, Han ZQ, Yan WD, Tang CZ, Xie JY, Chen H, Hu DY.

J Thorac Cardiovasc Surg. 2010 Sep;140(3):684-7. doi: 10.1016/j.jtcvs.2010.01.013. Epub 2010 Mar 26.

PubMed [citation]

PMID:: 20347099

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, SCV001565616.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces methionine with leucine at codon 310 of the GATA4 protein (p.Met310Leu). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and leucine. 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. This variant disrupts the p.Met310 amino acid residue in GATA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20347099). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GATA4-related conditions. This variant is not present in population databases (ExAC no frequency).

#	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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