NM_001100.4(ACTA1):c.1061T>C (p.Phe354Ser) AND Actin accumulation myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 18, 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:: RCV003517474.2

Allele description [Variation Report for NM_001100.4(ACTA1):c.1061T>C (p.Phe354Ser)]

NM_001100.4(ACTA1):c.1061T>C (p.Phe354Ser)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.13

Genomic location:

Preferred name:

NM_001100.4(ACTA1):c.1061T>C (p.Phe354Ser)

HGVS:

NC_000001.11:g.229431572A>G
NG_006672.1:g.7525T>C
NG_093759.1:g.577A>G
NM_001100.4:c.1061T>CMANE SELECT
NP_001091.1:p.Phe354Ser
NP_001091.1:p.Phe354Ser
LRG_429t1:c.1061T>C
LRG_429:g.7525T>C
LRG_429p1:p.Phe354Ser
NC_000001.10:g.229567319A>G
NM_001100.3:c.1061T>C

Protein change:

F354S

Molecular consequence:

NM_001100.4:c.1061T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Actin accumulation myopathy (CMYO2A)
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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292980	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 18, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19562689, 22358459, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292980

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 18, 2023)

germline

clinical testing

PubMed (3)
[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

Lindqvist J, Pénisson-Besnier I, Iwamoto H, Li M, Yagi N, Ochala J.

Acta Neuropathol. 2012 May;123(5):739-46. doi: 10.1007/s00401-012-0962-z. Epub 2012 Feb 23.

PubMed [citation]

PMID:: 22358459

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292980.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ACTA1 protein function. 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. This missense change has been observed in individuals with autosomal dominant nuclear myopathy (PMID: 19562689, 22358459). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 354 of the ACTA1 protein (p.Phe354Ser).

#	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: Sep 29, 2024

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