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NM_005159.5(ACTC1):c.28C>A (p.Leu10Met) AND multiple conditions

Germline classification:
Likely pathogenic (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:
RCV000576182.7

Allele description [Variation Report for NM_005159.5(ACTC1):c.28C>A (p.Leu10Met)]

NM_005159.5(ACTC1):c.28C>A (p.Leu10Met)

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.28C>A (p.Leu10Met)
Other names:
p.L10M:CTG>ATG
HGVS:
  • NC_000015.10:g.34794781G>T
  • NG_007553.1:g.5946C>A
  • NM_005159.5:c.28C>AMANE SELECT
  • NP_005150.1:p.Leu10Met
  • LRG_388t1:c.28C>A
  • LRG_388:g.5946C>A
  • NC_000015.9:g.35086982G>T
  • NM_005159.4:c.28C>A
  • c.28C>A
Protein change:
L10M
Links:
dbSNP: rs397517057
NCBI 1000 Genomes Browser:
rs397517057
Molecular consequence:
  • NM_005159.5:c.28C>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
SCV000676951Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 23, 2023) 		germlineclinical testing

PubMed (2)
[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

The role of caffeinated beverages in dental fluorosis.

Chan JT, Yip TT, Jeske AH.

Med Hypotheses. 1990 Sep;33(1):21-2.

PubMed [citation]
PMID:
2255271

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000676951.6

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 10 of the ACTC1 protein (p.Leu10Met). This variant is present in population databases (rs397517057, gnomAD 0.009%). This missense change has been observed in individuals with clinical features of hypertrophic cardiomyopathy (PMID: 2255271; Invitae). ClinVar contains an entry for this variant (Variation ID: 50936). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Mar 5, 2024