NM_001308093.3(GATA4):c.1243G>C (p.Val415Leu) AND Atrioventricular septal defect 4

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 13, 2023
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:: RCV003528454.3

Allele description [Variation Report for NM_001308093.3(GATA4):c.1243G>C (p.Val415Leu)]

NM_001308093.3(GATA4):c.1243G>C (p.Val415Leu)

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.1243G>C (p.Val415Leu)

HGVS:

NC_000008.11:g.11758386G>C
NG_008177.2:g.86468G>C
NM_001308093.3:c.1243G>CMANE SELECT
NM_001308094.2:c.622G>C
NM_001374273.1:c.622G>C
NM_001374274.1:c.496G>C
NM_002052.5:c.1240G>C
NP_001295022.1:p.Val415Leu
NP_001295023.1:p.Val208Leu
NP_001361202.1:p.Val208Leu
NP_001361203.1:p.Val166Leu
NP_002043.2:p.Val414Leu
NC_000008.10:g.11615895G>C
NM_002052.3:c.1240G>C

Protein change:

V166L

Molecular consequence:

NM_001308093.3:c.1243G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001308094.2:c.622G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374273.1:c.622G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001374274.1:c.496G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002052.5:c.1240G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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Bestrophin homolog [Caenorhabditis elegans]
Bestrophin homolog [Caenorhabditis elegans]
gi|133930976|ref|NP_502108.2|

Protein
Uncharacterized protein CELE_T02E1.7 [Caenorhabditis elegans]
Uncharacterized protein CELE_T02E1.7 [Caenorhabditis elegans]
gi|17508799|ref|NP_492235.1|

Protein
protein US26 [Panine betaherpesvirus 2]
protein US26 [Panine betaherpesvirus 2]
gi|20026756|ref|NP_612798.1|

Protein
PREDICTED: Orcinus orca collagen type XXV alpha 1 chain (COL25A1), transcript va...
PREDICTED: Orcinus orca collagen type XXV alpha 1 chain (COL25A1), transcript variant X2, mRNA
gi|2280703852|ref|XM_049709644.1|

Nucleotide
Caenorhabditis elegans Cuticlin-6 (cut-6), mRNA
Caenorhabditis elegans Cuticlin-6 (cut-6), mRNA
gi|1972265874|ref|NM_066999.8|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004368475	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 13, 2023)	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

SCV004368475

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 13, 2023)

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, SCV004368475.1

#	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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬† is likely to be tolerated. This variant has not been reported in the literature in individuals affected with GATA4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 414 of the GATA4 protein (p.Val414Leu).

#	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: Nov 10, 2024

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