NM_001100.4(ACTA1):c.1109C>A (p.Ser370Tyr) AND Actin accumulation myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 2017
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:: RCV000531952.7

Allele description [Variation Report for NM_001100.4(ACTA1):c.1109C>A (p.Ser370Tyr)]

NM_001100.4(ACTA1):c.1109C>A (p.Ser370Tyr)

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.1109C>A (p.Ser370Tyr)

HGVS:

NC_000001.11:g.229431524G>T
NG_006672.1:g.7573C>A
NM_001100.4:c.1109C>AMANE SELECT
NP_001091.1:p.Ser370Tyr
NP_001091.1:p.Ser370Tyr
LRG_429t1:c.1109C>A
LRG_429:g.7573C>A
LRG_429p1:p.Ser370Tyr
NC_000001.10:g.229567271G>T
NM_001100.3:c.1109C>A

Protein change:

S370Y

Links:

dbSNP: rs1553255290

NCBI 1000 Genomes Browser:

rs1553255290

Molecular consequence:

NM_001100.4:c.1109C>A - 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

Recent activity

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Mus musculus hypothetical protein E130207K11 (E130207K11), mRNA
Mus musculus hypothetical protein E130207K11 (E130207K11), mRNA
gi|27370453|ref|NM_172943.1|

Nucleotide
PREDICTED: Homo sapiens spermatogenesis associated 3 (SPATA3), transcript varian...
PREDICTED: Homo sapiens spermatogenesis associated 3 (SPATA3), transcript variant X9, misc_RNA
gi|2217325620|ref|XR_922856.3|

Nucleotide
Profile neighbors for GEO Profiles (Select 19352981) (185)
GEO Profiles
Model organism or animal sample from Canis latrans
Model organism or animal sample from Canis latrans

biosample
BioSample Links for SRA (Select 28766751) (1)
BioSample

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000638356	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000638356

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2017)

germline

clinical testing

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

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

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, SCV000638356.4

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with ACTA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with tyrosine at codon 370 of the ACTA1 protein (p.Ser370Tyr). The serine residue is highly conserved and there is a large physicochemical difference between serine and tyrosine.

#	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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