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NM_005159.5(ACTC1):c.532A>T (p.Met178Leu) AND Hypertrophic cardiomyopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 30, 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:
RCV004002623.2

Allele description [Variation Report for NM_005159.5(ACTC1):c.532A>T (p.Met178Leu)]

NM_005159.5(ACTC1):c.532A>T (p.Met178Leu)

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.532A>T (p.Met178Leu)
HGVS:
  • NC_000015.10:g.34792492T>A
  • NG_007553.1:g.8235A>T
  • NM_005159.5:c.532A>TMANE SELECT
  • NP_005150.1:p.Met178Leu
  • LRG_388t1:c.532A>T
  • LRG_388:g.8235A>T
  • NC_000015.9:g.35084693T>A
  • NM_005159.4:c.532A>T
Protein change:
M178L
Links:
dbSNP: rs1555418829
NCBI 1000 Genomes Browser:
rs1555418829
Molecular consequence:
  • NM_005159.5:c.532A>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004844832All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Nov 30, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

Exome sequencing identifies a novel variant in ACTC1 associated with familial atrial septal defect.

Greenway SC, McLeod R, Hume S, Roslin NM, Alvarez N, Giuffre M, Zhan SH, Shen Y, Preuss C, Andelfinger G; FORGE Canada Consortium., Jones SJ, Gerull B.

Can J Cardiol. 2014 Feb;30(2):181-7. doi: 10.1016/j.cjca.2013.12.003. Epub 2013 Dec 6.

PubMed [citation]
PMID:
24461919

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004844832.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

This missense variant replaces methionine with leucine at codon 178 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 five related individuals affected with atrial septal defect (PMID: 24461919). It has been shown that this variant segregates with disease in this family. This variant has not been identified 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024