NM_005751.5(AKAP9):c.11297G>A (p.Arg3766Gln) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 18, 2023
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:: RCV001309086.5

Allele description [Variation Report for NM_005751.5(AKAP9):c.11297G>A (p.Arg3766Gln)]

NM_005751.5(AKAP9):c.11297G>A (p.Arg3766Gln)

Gene:

AKAP9:A-kinase anchoring protein 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.2

Genomic location:

Preferred name:

NM_005751.5(AKAP9):c.11297G>A (p.Arg3766Gln)

HGVS:

NC_000007.14:g.92102793G>A
NG_011623.1:g.166919G>A
NM_001379277.1:c.5942G>A
NM_005751.4:c.11297G>A
NM_005751.5:c.11297G>AMANE SELECT
NM_147185.3:c.11273G>A
NP_001366206.1:p.Arg1981Gln
NP_005742.4:p.Arg3766Gln
NP_671714.1:p.Arg3758Gln
LRG_331t1:c.11297G>A
LRG_331:g.166919G>A
NC_000007.13:g.91732107G>A
NM_147185.2:c.11273G>A

Protein change:

R1981Q

Links:

dbSNP: rs137892407

NCBI 1000 Genomes Browser:

rs137892407

Molecular consequence:

NM_001379277.1:c.5942G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005751.5:c.11297G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_147185.3:c.11273G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Long QT syndrome (LQTS)
Identifiers:: MONDO: MONDO:0002442; MeSH: D008133; MedGen: C0023976

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001498568	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32233023, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001498568

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 18, 2023)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Wolff-Parkinson-White syndrome: De novo variants and evidence for mutational burden in genes associated with atrial fibrillation.

Coban-Akdemir ZH, Charng WL, Azamian M, Paine IS, Punetha J, Grochowski CM, Gambin T, Valdes SO, Cannon B, Zapata G, Hernandez PP, Jhangiani S, Doddapaneni H, Hu J, Boricha F, Muzny DM, Boerwinkle E, Yang Y, Gibbs RA, Posey JE, Wehrens XHT, Belmont JW, et al.

Am J Med Genet A. 2020 Jun;182(6):1387-1399. doi: 10.1002/ajmg.a.61571. Epub 2020 Mar 31.

PubMed [citation]

PMID:: 32233023
PMCID:: PMC7275694

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, SCV001498568.4

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 3766 of the AKAP9 protein (p.Arg3766Gln). This variant is present in population databases (rs137892407, gnomAD 0.05%). This missense change has been observed in individual(s) with AKAP9-related conditions (PMID: 32233023). This variant is also known as c.11273G>A, (p.Arg3758Gln). ClinVar contains an entry for this variant (Variation ID: 487596). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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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