NM_005159.5(ACTC1):c.475G>A (p.Asp159Asn) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 9, 2013
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:: RCV000038330.5

Allele description [Variation Report for NM_005159.5(ACTC1):c.475G>A (p.Asp159Asn)]

NM_005159.5(ACTC1):c.475G>A (p.Asp159Asn)

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.475G>A (p.Asp159Asn)

Other names:

p.D159N:GAT>AAT

HGVS:

NC_000015.10:g.34792549C>T
NG_007553.1:g.8178G>A
NM_005159.5:c.475G>AMANE SELECT
NP_005150.1:p.Asp159Asn
LRG_388t1:c.475G>A
LRG_388:g.8178G>A
NC_000015.9:g.35084750C>T
NM_005159.4:c.475G>A
c.475G>A

Protein change:

D159N

Links:

dbSNP: rs397517063

NCBI 1000 Genomes Browser:

rs397517063

Molecular consequence:

NM_005159.5:c.475G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000062001	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jan 9, 2013)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24503780, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000062001

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jan 9, 2013)

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	not provided	2	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062001.5

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

Description

The Asp159Asn variant in ACTC1 has not previously been reported in the literatur e but has been identified in one individual with DCM (this individual's mother) tested by our laboratory (LMM unpublished data). This variant has not been ident ified in large and broad European American and African American populations by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/), though it may be common in other populations. Computational analyses (biochemical amino a cid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the A sp159Asn variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, additional information is need ed to fully assess the clinical significance of the Asp159Asn 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		2	not provided	1	not provided

Last Updated: Mar 4, 2023

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