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NM_004100.5(EYA4):c.1223G>A (p.Arg408His) AND Dilated cardiomyopathy 1J

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 17, 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:
RCV001853452.6

Allele description [Variation Report for NM_004100.5(EYA4):c.1223G>A (p.Arg408His)]

NM_004100.5(EYA4):c.1223G>A (p.Arg408His)

Genes:
EYA4:EYA transcriptional coactivator and phosphatase 4 [Gene - OMIM - HGNC]
LOC126859796:MED14-independent group 3 enhancer GRCh37_chr6:133826289-133827488 [Gene]
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.1223G>A (p.Arg408His)
HGVS:
  • NC_000006.12:g.133506137G>A
  • NG_011596.2:g.269781G>A
  • NM_001301012.2:c.1061G>A
  • NM_001301013.2:c.1241G>A
  • NM_001370458.1:c.1154G>A
  • NM_001370459.1:c.1079G>A
  • NM_004100.5:c.1223G>AMANE SELECT
  • NM_172103.4:c.1154G>A
  • NM_172105.4:c.1223G>A
  • NP_001287941.1:p.Arg354His
  • NP_001287942.1:p.Arg414His
  • NP_001357387.1:p.Arg385His
  • NP_001357388.1:p.Arg360His
  • NP_004091.3:p.Arg408His
  • NP_742101.2:p.Arg385His
  • NP_742103.1:p.Arg408His
  • LRG_418t1:c.1223G>A
  • LRG_418:g.269781G>A
  • LRG_418p1:p.Arg408His
  • NC_000006.11:g.133827275G>A
  • NM_004100.4:c.1223G>A
  • NR_109982.1:n.2497C>T
Protein change:
R354H
Links:
dbSNP: rs760787542
NCBI 1000 Genomes Browser:
rs760787542
Molecular consequence:
  • NM_001301012.2:c.1061G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001301013.2:c.1241G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370458.1:c.1154G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001370459.1:c.1079G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004100.5:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172103.4:c.1154G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_172105.4:c.1223G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_109982.1:n.2497C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002187619Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 17, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction.

Miszalski-Jamka K, Jefferies JL, Mazur W, Głowacki J, Hu J, Lazar M, Gibbs RA, Liczko J, Kłyś J, Venner E, Muzny DM, Rycaj J, Białkowski J, Kluczewska E, Kalarus Z, Jhangiani S, Al-Khalidi H, Kukulski T, Lupski JR, Craigen WJ, Bainbridge MN.

Circ Cardiovasc Genet. 2017 Aug;10(4). doi: 10.1161/CIRCGENETICS.117.001763.

PubMed [citation]
PMID:
28798025
PMCID:
PMC5665372

Prevalence and clinical features of hearing loss caused by EYA4 variants.

Shinagawa J, Moteki H, Nishio SY, Ohyama K, Otsuki K, Iwasaki S, Masuda S, Oshikawa C, Ohta Y, Arai Y, Takahashi M, Sakuma N, Abe S, Sakurai Y, Sakaguchi H, Ishino T, Uehara N, Usami SI.

Sci Rep. 2020 Feb 27;10(1):3662. doi: 10.1038/s41598-020-60259-0.

PubMed [citation]
PMID:
32107406
PMCID:
PMC7046659
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002187619.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 408 of the EYA4 protein (p.Arg408His). This variant is present in population databases (rs760787542, gnomAD 0.008%). This missense change has been observed in individual(s) with EYA4-related conditions (PMID: 28798025, 32107406, 32277154). ClinVar contains an entry for this variant (Variation ID: 228680). 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) performed at Invitae indicates that this missense variant is not expected to disrupt EYA4 protein function with a negative predictive value of 80%. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024