NM_005159.5(ACTC1):c.616+1G>A AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 3, 2010
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:: RCV000038334.5

Allele description [Variation Report for NM_005159.5(ACTC1):c.616+1G>A]

NM_005159.5(ACTC1):c.616+1G>A

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.616+1G>A

HGVS:

NC_000015.10:g.34792407C>T
NG_007553.1:g.8320G>A
NM_001406482.1:c.616+1G>A
NM_001406483.1:c.616+1G>A
NM_001406484.1:c.481+1G>A
NM_001406485.1:c.175+1G>A
NM_005159.5:c.616+1G>AMANE SELECT
LRG_388t1:c.616+1G>A
LRG_388:g.8320G>A
NC_000015.9:g.35084608C>T
NM_005159.4:c.616+1G>A
c.616+1G>A

Links:

dbSNP: rs111904141

NCBI 1000 Genomes Browser:

rs111904141

Molecular consequence:

NM_001406482.1:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406483.1:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406484.1:c.481+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406485.1:c.175+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_005159.5:c.616+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

PREDICTED: Cololabis saira acetylcholine receptor subunit alpha-like (LOC1334459...
PREDICTED: Cololabis saira acetylcholine receptor subunit alpha-like (LOC133445930), mRNA
gi|2638989579|ref|XM_061723500.1|

Nucleotide
PREDICTED: Dendroctonus ponderosae uncharacterized LOC109541812 (LOC109541812), ...
PREDICTED: Dendroctonus ponderosae uncharacterized LOC109541812 (LOC109541812), transcript variant X2, mRNA
gi|2252289276|ref|XM_019910786.2|

Nucleotide
Homo sapiens RFX5 antisense RNA 1 (RFX5-AS1), long non-coding RNA
Homo sapiens RFX5 antisense RNA 1 (RFX5-AS1), long non-coding RNA
gi|822885249|ref|NR_131972.1|

Nucleotide

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
SCV000062005	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Nov 3, 2010)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9114002, 17947298, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000062005

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Nov 3, 2010)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin.

Kumar A, Crawford K, Close L, Madison M, Lorenz J, Doetschman T, Pawlowski S, Duffy J, Neumann J, Robbins J, Boivin GP, O'Toole BA, Lessard JL.

Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4406-11.

PubMed [citation]

PMID:: 9114002
PMCID:: PMC20735

Alpha-cardiac actin mutations produce atrial septal defects.

Matsson H, Eason J, Bookwalter CS, Klar J, Gustavsson P, Sunnegårdh J, Enell H, Jonzon A, Vikkula M, Gutierrez I, Granados-Riveron J, Pope M, Bu'Lock F, Cox J, Robinson TE, Song F, Brook DJ, Marston S, Trybus KM, Dahl N.

Hum Mol Genet. 2008 Jan 15;17(2):256-65. Epub 2007 Oct 18.

PubMed [citation]

PMID:: 17947298

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062005.5

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

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The 616+1G>A va riant has not been reported in the literature. This variant is predicted to cau se abnormal splicing because the nucleotide substitution occurs in the highly co nserved splice consensus sequence. Splice variants can lead to aberrant, truncat ed, or absent protein and in most genes, are typically assumed to be disease cau sing. However, all disease causing variants in the ACTC gene known to date are missense variants and it is therefore unclear whether abnormal splicing can lead to disease. However, this individual's racial origin is reported to be Caucasia n and the 616+1G>A variant has not been identified in over 1500 Caucasian proban ds (3000 chromosomes) tested by our laboratory. Although we cannot exclude the p ossibility that this variant could be benign, this low frequency increases the l ikelihood that it is pathogenic. In summary, additional studies (healthy control studies and/or family studies) are necessary to determine the significance of t he 616+1 variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: Jun 10, 2023

ClinVar

Relating variation to medicine