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NM_005159.5(ACTC1):c.635G>A (p.Arg212His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 23, 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:
RCV001057276.8

Allele description [Variation Report for NM_005159.5(ACTC1):c.635G>A (p.Arg212His)]

NM_005159.5(ACTC1):c.635G>A (p.Arg212His)

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.635G>A (p.Arg212His)
HGVS:
  • NC_000015.10:g.34792263C>T
  • NG_007553.1:g.8464G>A
  • NM_005159.5:c.635G>AMANE SELECT
  • NP_005150.1:p.Arg212His
  • LRG_388t1:c.635G>A
  • LRG_388:g.8464G>A
  • NC_000015.9:g.35084464C>T
  • NM_005159.4:c.635G>A
  • c.635G>A
Protein change:
R212H
Links:
dbSNP: rs397517067
NCBI 1000 Genomes Browser:
rs397517067
Molecular consequence:
  • NM_005159.5:c.635G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy 11
Synonyms:
Familial hypertrophic cardiomyopathy 11; ACTC1-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MONDO: MONDO:0012799; MedGen: C2677506; OMIM: 612098
Name:
Dilated cardiomyopathy 1R (CMD1R)
Identifiers:
MONDO: MONDO:0013261; MedGen: C3150681; Orphanet: 154; Orphanet: 54260; OMIM: 613424
Name:
Atrial septal defect 5 (ASD5)
Identifiers:
MONDO: MONDO:0013011; MedGen: C2748552; Orphanet: 1478; OMIM: 612794

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001221760Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 23, 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

Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management.

Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, He W, Dharmadhikari AV, Qu C, Ward P, Braxton A, Narayanan S, Ge X, Tokita MJ, Santiago-Sim T, Dai H, Chiang T, Smith H, Azamian MS, Robak L, Bostwick BL, et al.

JAMA Pediatr. 2017 Dec 4;171(12):e173438. doi: 10.1001/jamapediatrics.2017.3438. Epub 2017 Dec 4.

PubMed [citation]
PMID:
28973083
PMCID:
PMC6359927

A burden of sarcomere gene variants in fetal-onset patients with left ventricular noncompaction.

Hirono K, Hata Y, Ozawa SW, Toda T, Momoi N, Fukuda Y, Inuzuka R, Nagamine H, Sakaguchi H, Kurosaki K, Okabe M, Takarada S, Miyao N, Nakaoka H, Ibuki K, Origasa H, Bowles NE, Nishida N, Ichida F; for LVNC study collaborators..

Int J Cardiol. 2021 Apr 1;328:122-129. doi: 10.1016/j.ijcard.2020.12.013. Epub 2020 Dec 10.

PubMed [citation]
PMID:
33309763
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001221760.5

#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 212 of the ACTC1 protein (p.Arg212His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 28973083, 33309763, 33500567). ClinVar contains an entry for this variant (Variation ID: 45186). 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 ACTC1 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: Oct 20, 2024