NM_001148.6(ANK2):c.1177G>A (p.Ala393Thr) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: May 30, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000171736.2

Allele description [Variation Report for NM_001148.6(ANK2):c.1177G>A (p.Ala393Thr)]

NM_001148.6(ANK2):c.1177G>A (p.Ala393Thr)

Gene:
ANK2:ankyrin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q26
Genomic location:
Preferred name:
NM_001148.6(ANK2):c.1177G>A (p.Ala393Thr)
HGVS:
  • NC_000004.12:g.113255921G>A
  • NG_009006.2:g.442839G>A
  • NM_001127493.2:c.1114G>A
  • NM_001148.6:c.1177G>AMANE SELECT
  • NM_001354225.1:c.1177G>A
  • NM_001354228.1:c.1177G>A
  • NM_001354230.1:c.1222G>A
  • NM_001354231.1:c.1222G>A
  • NM_001354232.1:c.1177G>A
  • NM_001354235.1:c.1177G>A
  • NM_001354236.1:c.1177G>A
  • NM_001354237.1:c.1222G>A
  • NM_001354239.1:c.1114G>A
  • NM_001354240.1:c.1222G>A
  • NM_001354241.1:c.1222G>A
  • NM_001354242.1:c.1222G>A
  • NM_001354243.1:c.1114G>A
  • NM_001354244.1:c.1114G>A
  • NM_001354245.1:c.1177G>A
  • NM_001354246.1:c.1177G>A
  • NM_001354249.1:c.1090G>A
  • NM_001354252.1:c.1114G>A
  • NM_001354253.1:c.1114G>A
  • NM_001354254.1:c.1114G>A
  • NM_001354255.1:c.1114G>A
  • NM_001354256.1:c.1114G>A
  • NM_001354257.1:c.1114G>A
  • NM_001354258.1:c.1177G>A
  • NM_001354260.1:c.1090G>A
  • NM_001354261.1:c.1135G>A
  • NM_001354262.1:c.1114G>A
  • NM_001354264.1:c.1090G>A
  • NM_001354265.1:c.1177G>A
  • NM_001354266.1:c.1090G>A
  • NM_001354267.1:c.1090G>A
  • NM_001354268.1:c.1177G>A
  • NM_001354269.1:c.1165G>A
  • NM_001354270.1:c.1114G>A
  • NM_001354271.1:c.1090G>A
  • NM_001354272.1:c.1114G>A
  • NM_001354273.1:c.1177G>A
  • NM_001354274.1:c.1090G>A
  • NM_001354275.1:c.1114G>A
  • NM_001354276.1:c.1090G>A
  • NM_001354277.1:c.1090G>A
  • NM_020977.4:c.1177G>A
  • NP_001120965.1:p.Ala372Thr
  • NP_001139.3:p.Ala393Thr
  • NP_001341154.1:p.Ala393Thr
  • NP_001341157.1:p.Ala393Thr
  • NP_001341159.1:p.Ala408Thr
  • NP_001341160.1:p.Ala408Thr
  • NP_001341161.1:p.Ala393Thr
  • NP_001341164.1:p.Ala393Thr
  • NP_001341165.1:p.Ala393Thr
  • NP_001341166.1:p.Ala408Thr
  • NP_001341168.1:p.Ala372Thr
  • NP_001341169.1:p.Ala408Thr
  • NP_001341170.1:p.Ala408Thr
  • NP_001341171.1:p.Ala408Thr
  • NP_001341172.1:p.Ala372Thr
  • NP_001341173.1:p.Ala372Thr
  • NP_001341174.1:p.Ala393Thr
  • NP_001341175.1:p.Ala393Thr
  • NP_001341178.1:p.Ala364Thr
  • NP_001341181.1:p.Ala372Thr
  • NP_001341182.1:p.Ala372Thr
  • NP_001341183.1:p.Ala372Thr
  • NP_001341184.1:p.Ala372Thr
  • NP_001341185.1:p.Ala372Thr
  • NP_001341186.1:p.Ala372Thr
  • NP_001341187.1:p.Ala393Thr
  • NP_001341189.1:p.Ala364Thr
  • NP_001341190.1:p.Ala379Thr
  • NP_001341191.1:p.Ala372Thr
  • NP_001341193.1:p.Ala364Thr
  • NP_001341194.1:p.Ala393Thr
  • NP_001341195.1:p.Ala364Thr
  • NP_001341196.1:p.Ala364Thr
  • NP_001341197.1:p.Ala393Thr
  • NP_001341198.1:p.Ala389Thr
  • NP_001341199.1:p.Ala372Thr
  • NP_001341200.1:p.Ala364Thr
  • NP_001341201.1:p.Ala372Thr
  • NP_001341202.1:p.Ala393Thr
  • NP_001341203.1:p.Ala364Thr
  • NP_001341204.1:p.Ala372Thr
  • NP_001341205.1:p.Ala364Thr
  • NP_001341206.1:p.Ala364Thr
  • NP_066187.2:p.Ala393Thr
  • LRG_327t1:c.1177G>A
  • LRG_327:g.442839G>A
  • NC_000004.11:g.114177077G>A
  • NM_001148.4:c.1177G>A
Protein change:
A364T
Links:
dbSNP: rs147458476
NCBI 1000 Genomes Browser:
rs147458476
Molecular consequence:
  • NM_001127493.2:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001148.6:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354225.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354228.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354230.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354231.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354232.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354235.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354236.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354237.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354239.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354240.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354241.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354242.1:c.1222G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354243.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354244.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354245.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354246.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354249.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354252.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354253.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354254.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354255.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354256.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354257.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354258.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354260.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354261.1:c.1135G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354262.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354264.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354265.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354266.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354267.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354268.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354269.1:c.1165G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354270.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354271.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354272.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354273.1:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354274.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354275.1:c.1114G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354276.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354277.1:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020977.4:c.1177G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000055182Biesecker Lab/Clinical Genomics Section,National Institutes of Health - ClinSeqcriteria provided, single submitter
Likely benign
(Jun 24, 2013)
unknownresearch

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

SCV000583306GeneDxcriteria provided, single submitter
Uncertain significance
(May 30, 2017)
germlineclinical testing

Citation Link

Description

The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details.

SCV000055182

Medical sequencing

SCV000055182

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknown1not providednot providednot providednot providedresearch

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]
PMID:
23861362
PMCID:
PMC3887521

Details of each submission

From Biesecker Lab/Clinical Genomics Section,National Institutes of Health - ClinSeq, SCV000055182.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000583306.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A variant of uncertain significance has been identified in the ANK2 gene. The A393T variant has not been previously published in association with arrhythmia to our knowledge. However, it has been observed in one individual from a cohort of individuals not selected for a history of cardiomyopathy, arrhythmia or family history of sudden cardiac death who underwent exome sequencing (Ng et al., 2013). Additionally, this variant has been observed in 8/8624 (0.09%) alleles from individuals of African ancestry, and 11/66346 (0.02%) alleles from individuals of Non-Finnish European ancestry, in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Nevertheless, the A393T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, this substitution occurs at a position that is largely conserved across species, although threonine (T) is the wild-type residue at this position in one non-mammalian species.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 12, 2021

Support Center