NM_005159.5(ACTC1):c.623G>A (p.Arg208His) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 26, 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:: RCV001182797.4

Allele description [Variation Report for NM_005159.5(ACTC1):c.623G>A (p.Arg208His)]

NM_005159.5(ACTC1):c.623G>A (p.Arg208His)

Genes:

GJD2-DT:GJD2 divergent transcript [Gene - HGNC]
ACTC1:actin alpha cardiac muscle 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q14

Genomic location:

Preferred name:

NM_005159.5(ACTC1):c.623G>A (p.Arg208His)

HGVS:

NC_000015.10:g.34792275C>T
NG_007553.1:g.8452G>A
NM_005159.5:c.623G>AMANE SELECT
NP_005150.1:p.Arg208His
LRG_388t1:c.623G>A
LRG_388:g.8452G>A
NC_000015.9:g.35084476C>T
NM_005159.4:c.623G>A

Protein change:

R208H

Links:

dbSNP: rs142839840

NCBI 1000 Genomes Browser:

rs142839840

Molecular consequence:

NM_005159.5:c.623G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001348386	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 26, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 28416588, 28798025, 30471092, 30847666, 32880476, 34935411, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001348386

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 26, 2023)

germline

clinical testing

PubMed (7)
[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

Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.

Dal Ferro M, Stolfo D, Altinier A, Gigli M, Perrieri M, Ramani F, Barbati G, Pivetta A, Brun F, Monserrat L, Giacca M, Mestroni L, Merlo M, Sinagra G.

Heart. 2017 Nov;103(21):1704-1710. doi: 10.1136/heartjnl-2016-311017. Epub 2017 Apr 17.

PubMed [citation]

PMID:: 28416588

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:pii: e001763. 10.1161/CIRCGENETICS.117.001763.

PubMed [citation]

PMID:: 28798025
PMCID:: PMC5665372

See all PubMed Citations (7)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001348386.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This missense variant replaces arginine with histidine at codon 208 of the ACTC1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in four individuals affected with dilated cardiomyopathy (PMID: 28416588, 30847666, 32880476 and 34935411) and two individuals affected with left ventricular non-compaction (PMID: 28798025, 30471092). This variant has been identified in 10/251470 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: May 19, 2024

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