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NM_001148.6(ANK2):c.11716C>T (p.Arg3906Trp) AND not specified

Germline classification:
Benign (1 submission)
Last evaluated:
Apr 8, 2019
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:
RCV000211890.13

Allele description [Variation Report for NM_001148.6(ANK2):c.11716C>T (p.Arg3906Trp)]

NM_001148.6(ANK2):c.11716C>T (p.Arg3906Trp)

Gene:
ANK2:ankyrin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q26
Genomic location:
Preferred name:
NM_001148.6(ANK2):c.11716C>T (p.Arg3906Trp)
Other names:
p.R3906W:CGG>TGG
HGVS:
  • NC_000004.12:g.113373306C>T
  • NG_009006.2:g.560224C>T
  • NM_001127493.3:c.5434C>T
  • NM_001148.6:c.11716C>TMANE SELECT
  • NM_001354225.2:c.5473C>T
  • NM_001354228.2:c.5455C>T
  • NM_001354230.2:c.5440C>T
  • NM_001354231.2:c.5596C>T
  • NM_001354232.2:c.5590C>T
  • NM_001354235.2:c.5551C>T
  • NM_001354236.2:c.5359C>T
  • NM_001354237.2:c.5539C>T
  • NM_001354239.2:c.5524C>T
  • NM_001354240.2:c.5506C>T
  • NM_001354241.2:c.5506C>T
  • NM_001354242.2:c.5503C>T
  • NM_001354243.2:c.5491C>T
  • NM_001354244.2:c.5488C>T
  • NM_001354245.2:c.5299C>T
  • NM_001354246.2:c.5458C>T
  • NM_001354249.2:c.5275C>T
  • NM_001354252.2:c.5431C>T
  • NM_001354253.2:c.5236C>T
  • NM_001354254.2:c.5410C>T
  • NM_001354255.2:c.5398C>T
  • NM_001354256.2:c.5395C>T
  • NM_001354257.2:c.5200C>T
  • NM_001354258.2:c.5362C>T
  • NM_001354260.2:c.5176C>T
  • NM_001354261.2:c.5320C>T
  • NM_001354262.2:c.5299C>T
  • NM_001354264.2:c.5296C>T
  • NM_001354265.2:c.5436+133C>T
  • NM_001354266.2:c.5275C>T
  • NM_001354267.2:c.5275C>T
  • NM_001354268.2:c.5263C>T
  • NM_001354269.3:c.5248C>T
  • NM_001354270.2:c.5236C>T
  • NM_001354271.2:c.5176C>T
  • NM_001354272.2:c.5310+133C>T
  • NM_001354273.2:c.5161C>T
  • NM_001354274.2:c.5298+133C>T
  • NM_001354275.2:c.5277+133C>T
  • NM_001354276.2:c.5253+133C>T
  • NM_001354277.2:c.5055+133C>T
  • NM_001354278.2:c.2989C>T
  • NM_001354279.2:c.3025C>T
  • NM_001354280.2:c.3010C>T
  • NM_001354281.2:c.2989C>T
  • NM_001354282.2:c.3003+133C>T
  • NM_001386142.1:c.11482C>T
  • NM_001386143.1:c.5491C>T
  • NM_001386144.1:c.5599C>T
  • NM_001386146.1:c.5335C>T
  • NM_001386147.1:c.5287C>T
  • NM_001386148.2:c.5446C>T
  • NM_001386149.1:c.5242C>T
  • NM_001386150.1:c.5335C>T
  • NM_001386151.1:c.5269C>T
  • NM_001386152.1:c.5412+3501C>T
  • NM_001386153.1:c.5242C>T
  • NM_001386154.1:c.5227C>T
  • NM_001386156.1:c.5200C>T
  • NM_001386157.1:c.5077C>T
  • NM_001386158.1:c.4978C>T
  • NM_001386160.1:c.5305C>T
  • NM_001386161.1:c.5395C>T
  • NM_001386162.1:c.5253+133C>T
  • NM_001386166.1:c.8116C>T
  • NM_001386167.1:c.1954C>T
  • NM_001386174.1:c.11950C>T
  • NM_001386175.1:c.11926C>T
  • NM_001386186.2:c.5446C>T
  • NM_001386187.2:c.5326C>T
  • NM_020977.5:c.5461C>T
  • NP_001120965.1:p.Arg1812Trp
  • NP_001139.3:p.Arg3906Trp
  • NP_001341154.1:p.Arg1825Trp
  • NP_001341157.1:p.Arg1819Trp
  • NP_001341159.1:p.Arg1814Trp
  • NP_001341160.1:p.Arg1866Trp
  • NP_001341161.1:p.Arg1864Trp
  • NP_001341164.1:p.Arg1851Trp
  • NP_001341165.1:p.Arg1787Trp
  • NP_001341166.1:p.Arg1847Trp
  • NP_001341168.1:p.Arg1842Trp
  • NP_001341169.1:p.Arg1836Trp
  • NP_001341170.1:p.Arg1836Trp
  • NP_001341171.1:p.Arg1835Trp
  • NP_001341172.1:p.Arg1831Trp
  • NP_001341173.1:p.Arg1830Trp
  • NP_001341174.1:p.Arg1767Trp
  • NP_001341175.1:p.Arg1820Trp
  • NP_001341178.1:p.Arg1759Trp
  • NP_001341181.1:p.Arg1811Trp
  • NP_001341182.1:p.Arg1746Trp
  • NP_001341183.1:p.Arg1804Trp
  • NP_001341184.1:p.Arg1800Trp
  • NP_001341185.1:p.Arg1799Trp
  • NP_001341186.1:p.Arg1734Trp
  • NP_001341187.1:p.Arg1788Trp
  • NP_001341189.1:p.Arg1726Trp
  • NP_001341190.1:p.Arg1774Trp
  • NP_001341191.1:p.Arg1767Trp
  • NP_001341193.1:p.Arg1766Trp
  • NP_001341195.1:p.Arg1759Trp
  • NP_001341196.1:p.Arg1759Trp
  • NP_001341197.1:p.Arg1755Trp
  • NP_001341198.1:p.Arg1750Trp
  • NP_001341199.1:p.Arg1746Trp
  • NP_001341200.1:p.Arg1726Trp
  • NP_001341202.1:p.Arg1721Trp
  • NP_001341207.1:p.Arg997Trp
  • NP_001341208.1:p.Arg1009Trp
  • NP_001341209.1:p.Arg1004Trp
  • NP_001341210.1:p.Arg997Trp
  • NP_001373071.1:p.Arg3828Trp
  • NP_001373072.1:p.Arg1831Trp
  • NP_001373073.1:p.Arg1867Trp
  • NP_001373075.1:p.Arg1779Trp
  • NP_001373076.1:p.Arg1763Trp
  • NP_001373077.1:p.Arg1816Trp
  • NP_001373078.1:p.Arg1748Trp
  • NP_001373079.1:p.Arg1779Trp
  • NP_001373080.1:p.Arg1757Trp
  • NP_001373082.1:p.Arg1748Trp
  • NP_001373083.1:p.Arg1743Trp
  • NP_001373085.1:p.Arg1734Trp
  • NP_001373086.1:p.Arg1693Trp
  • NP_001373087.1:p.Arg1660Trp
  • NP_001373089.1:p.Arg1769Trp
  • NP_001373090.1:p.Arg1799Trp
  • NP_001373095.1:p.Arg2706Trp
  • NP_001373096.1:p.Arg652Trp
  • NP_001373103.1:p.Arg3984Trp
  • NP_001373104.1:p.Arg3976Trp
  • NP_001373115.1:p.Arg1816Trp
  • NP_001373116.1:p.Arg1776Trp
  • NP_066187.2:p.Arg1821Trp
  • LRG_327t1:c.11716C>T
  • LRG_327:g.560224C>T
  • NC_000004.11:g.114294462C>T
  • NM_001148.4:c.11716C>T
  • Q01484:p.Arg3906Trp
Protein change:
R1004W; ARG1788TRP
Links:
UniProtKB: Q01484#VAR_022937; OMIM: 106410.0004; dbSNP: rs121912706
NCBI 1000 Genomes Browser:
rs121912706
Molecular consequence:
  • NM_001354265.2:c.5436+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354272.2:c.5310+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354274.2:c.5298+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354275.2:c.5277+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354276.2:c.5253+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354277.2:c.5055+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354282.2:c.3003+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386152.1:c.5412+3501C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001386162.1:c.5253+133C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001127493.3:c.5434C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001148.6:c.11716C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354225.2:c.5473C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354228.2:c.5455C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354230.2:c.5440C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354231.2:c.5596C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354232.2:c.5590C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354235.2:c.5551C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354236.2:c.5359C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354237.2:c.5539C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354239.2:c.5524C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354240.2:c.5506C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354241.2:c.5506C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354242.2:c.5503C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354243.2:c.5491C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354244.2:c.5488C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354245.2:c.5299C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354246.2:c.5458C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354249.2:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354252.2:c.5431C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354253.2:c.5236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354254.2:c.5410C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354255.2:c.5398C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354256.2:c.5395C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354257.2:c.5200C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354258.2:c.5362C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354260.2:c.5176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354261.2:c.5320C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354262.2:c.5299C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354264.2:c.5296C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354266.2:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354267.2:c.5275C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354268.2:c.5263C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354269.3:c.5248C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354270.2:c.5236C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354271.2:c.5176C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354273.2:c.5161C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354278.2:c.2989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354279.2:c.3025C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354280.2:c.3010C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354281.2:c.2989C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386142.1:c.11482C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386143.1:c.5491C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386144.1:c.5599C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386146.1:c.5335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386147.1:c.5287C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386148.2:c.5446C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386149.1:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386150.1:c.5335C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386151.1:c.5269C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386153.1:c.5242C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386154.1:c.5227C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386156.1:c.5200C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386157.1:c.5077C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386158.1:c.4978C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386160.1:c.5305C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386161.1:c.5395C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386166.1:c.8116C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386167.1:c.1954C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386174.1:c.11950C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386175.1:c.11926C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386186.2:c.5446C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386187.2:c.5326C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020977.5:c.5461C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001363525Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Benign
(Apr 8, 2019) 		germlineclinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A cardiac arrhythmia syndrome caused by loss of ankyrin-B function.

Mohler PJ, Splawski I, Napolitano C, Bottelli G, Sharpe L, Timothy K, Priori SG, Keating MT, Bennett V.

Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9137-42. Epub 2004 Jun 3.

PubMed [citation]
PMID:
15178757
PMCID:
PMC428486

Targeted mutational analysis of ankyrin-B in 541 consecutive, unrelated patients referred for long QT syndrome genetic testing and 200 healthy subjects.

Sherman J, Tester DJ, Ackerman MJ.

Heart Rhythm. 2005 Nov;2(11):1218-23.

PubMed [citation]
PMID:
16253912
See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363525.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

Variant summary: ANK2 c.11716C>T (p.Arg3906Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 276816 control chromosomes, predominantly at a frequency of 0.0018 within the Non-Finnish European subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 270 fold of the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Long QT Syndrome (LQTS) phenotype (6.7e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. Mohler et al (2004) originally reported the variant in one LQTS proband from one family without segregation analysis performed, and also, the proband of another family with unknown/uncertain LQTS phenotype and her father who was asymptomatic. This study predates the emergence of large control population datasets. Subsequently, c.11716C>T has been reported in the literature in individuals affected with LQTS and hypertrophic cardiomyopathy and also, in a stillbirth case (Sahlin_2019, Lopes_2015, Sherman_2015, Lieve_2013, Ng_2013). A co-occurrence with a pathogenic variant causative of LQT syndrome has been reported at our laboratory (KCNQ1, c.1663C>T, p.Arg555Cys), providing supporting evidence for a benign role. Experimental evidence evaluating an impact on protein function demonstrated the variant to abolish ability of ankyrin-B to restore abnormal calcium dynamics and abnormal localization and expression of Na/Ca exchanger, Na/K ATPase, and InsP3R in mouse cardiomyocytes (Mohler_2004). However, it is not evident how these outcomes correlate to incidence of disease in human. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (2x), uncertain significance (1x) and once as pathogenic. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Dec 22, 2024