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NM_005159.5(ACTC1):c.375G>C (p.Met125Ile) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 9, 2018
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:
RCV000816559.7

Allele description [Variation Report for NM_005159.5(ACTC1):c.375G>C (p.Met125Ile)]

NM_005159.5(ACTC1):c.375G>C (p.Met125Ile)

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.375G>C (p.Met125Ile)
HGVS:
  • NC_000015.10:g.34793324C>G
  • NG_007553.1:g.7403G>C
  • NM_005159.5:c.375G>CMANE SELECT
  • NP_005150.1:p.Met125Ile
  • LRG_388t1:c.375G>C
  • LRG_388:g.7403G>C
  • NC_000015.9:g.35085525C>G
  • NM_005159.4:c.375G>C
Protein change:
M125I
Links:
dbSNP: rs1595761338
NCBI 1000 Genomes Browser:
rs1595761338
Molecular consequence:
  • NM_005159.5:c.375G>C - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000957074Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jul 9, 2018)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000957074.4

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

Description

This sequence change replaces methionine with isoleucine at codon 125 of the ACTC1 protein (p.Met125Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ACTC1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 13, 2024