NM_004100.5(EYA4):c.1434G>T (p.Met478Ile) AND Dilated cardiomyopathy 1J

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 3, 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:: RCV000641932.5

Allele description [Variation Report for NM_004100.5(EYA4):c.1434G>T (p.Met478Ile)]

NM_004100.5(EYA4):c.1434G>T (p.Met478Ile)

Genes:

EYA4:EYA transcriptional coactivator and phosphatase 4 [Gene - OMIM - HGNC]
TARID:TCF21 antisense RNA inducing promoter demethylation [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q23.2

Genomic location:

Preferred name:

NM_004100.5(EYA4):c.1434G>T (p.Met478Ile)

HGVS:

NC_000006.12:g.133512971G>T
NG_011596.2:g.276615G>T
NM_001301012.2:c.1272G>T
NM_001301013.2:c.1452G>T
NM_001370458.1:c.1365G>T
NM_001370459.1:c.1290G>T
NM_004100.5:c.1434G>TMANE SELECT
NM_172103.4:c.1365G>T
NM_172105.4:c.1434G>T
NP_001287941.1:p.Met424Ile
NP_001287942.1:p.Met484Ile
NP_001357387.1:p.Met455Ile
NP_001357388.1:p.Met430Ile
NP_004091.3:p.Met478Ile
NP_742101.2:p.Met455Ile
NP_742103.1:p.Met478Ile
LRG_418t1:c.1434G>T
LRG_418:g.276615G>T
LRG_418p1:p.Met478Ile
NC_000006.11:g.133834109G>T
NM_004100.4:c.1434G>T

Protein change:

M424I

Links:

dbSNP: rs1187396214

NCBI 1000 Genomes Browser:

rs1187396214

Molecular consequence:

NM_001301012.2:c.1272G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001301013.2:c.1452G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370458.1:c.1365G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001370459.1:c.1290G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004100.5:c.1434G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172103.4:c.1365G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172105.4:c.1434G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1J (CMD1J)
Synonyms:: CARDIOMYOPATHY, DILATED, WITH SENSORINEURAL HEARING LOSS, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0011541; MedGen: C1854368; Orphanet: 217622; OMIM: 605362

Recent activity

Clear Turn Off Turn On

esv34033 (0)
GEO DataSets
Serratia sp. JG-4-2 16S ribosomal RNA gene, partial sequence
Serratia sp. JG-4-2 16S ribosomal RNA gene, partial sequence
gi|359744439|gb|JN381535.1|

Nucleotide
Homo sapiens thioredoxin domain containing 11, mRNA (cDNA clone IMAGE:3864677), ...
Homo sapiens thioredoxin domain containing 11, mRNA (cDNA clone IMAGE:3864677), complete cds
gi|15489247|gb|BC013727.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000763582	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 3, 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

SCV000763582

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 3, 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, SCV000763582.4

#	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on EYA4 protein function. ClinVar contains an entry for this variant (Variation ID: 534388). This variant has not been reported in the literature in individuals affected with EYA4-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 478 of the EYA4 protein (p.Met478Ile).

#	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

ClinVar

Relating variation to medicine