NM_001100.4(ACTA1):c.400del (p.Met134fs) AND Actin accumulation myopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 19, 2021
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:: RCV002035327.3

Allele description [Variation Report for NM_001100.4(ACTA1):c.400del (p.Met134fs)]

NM_001100.4(ACTA1):c.400del (p.Met134fs)

Gene:

ACTA1:actin alpha 1, skeletal muscle [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q42.13

Genomic location:

Preferred name:

NM_001100.4(ACTA1):c.400del (p.Met134fs)

HGVS:

NC_000001.11:g.229432610del
NG_006672.1:g.6487del
NM_001100.4:c.400delMANE SELECT
NP_001091.1:p.Met134fs
LRG_429:g.6487del
NC_000001.10:g.229568357del

Protein change:

M134fs

Links:

dbSNP: rs2102736194

NCBI 1000 Genomes Browser:

rs2102736194

Molecular consequence:

NM_001100.4:c.400del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Actin accumulation myopathy (CMYP2A)
Synonyms:: Nemaline myopathy caused by mutation in the alpha-actin gene; CONGENITAL MYOPATHY 2A, TYPICAL, AUTOSOMAL DOMINANT; Myopathy, actin, congenital, with cores; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008070; MedGen: C3711389; OMIM: 161800

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002236935	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 19, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19562689, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236935

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 19, 2021)

germline

clinical testing

PubMed (2)
[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

Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1).

Laing NG, Dye DE, Wallgren-Pettersson C, Richard G, Monnier N, Lillis S, Winder TL, Lochmüller H, Graziano C, Mitrani-Rosenbaum S, Twomey D, Sparrow JC, Beggs AH, Nowak KJ.

Hum Mutat. 2009 Sep;30(9):1267-77. doi: 10.1002/humu.21059.

PubMed [citation]

PMID:: 19562689
PMCID:: PMC2784950

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, SCV002236935.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with ACTA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met134Cysfs*58) in the ACTA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACTA1 are known to be pathogenic (PMID: 19562689).

#	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: Feb 14, 2024

ClinVar

Relating variation to medicine