NM_005751.5(AKAP9):c.3448C>T (p.Leu1150Phe) AND Long QT syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 26, 2024
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:: RCV001923357.7

Allele description [Variation Report for NM_005751.5(AKAP9):c.3448C>T (p.Leu1150Phe)]

NM_005751.5(AKAP9):c.3448C>T (p.Leu1150Phe)

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.3448C>T (p.Leu1150Phe)

HGVS:

NC_000007.14:g.92012558C>T
NG_011623.1:g.76684C>T
NM_005751.5:c.3448C>TMANE SELECT
NM_147185.3:c.3448C>T
NP_005742.4:p.Leu1150Phe
NP_671714.1:p.Leu1150Phe
LRG_331:g.76684C>T
NC_000007.13:g.91641872C>T
NM_005751.4:c.3448C>T

Protein change:

L1150F

Links:

dbSNP: rs750350575

NCBI 1000 Genomes Browser:

rs750350575

Molecular consequence:

NM_005751.5:c.3448C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_147185.3:c.3448C>T - 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
SCV002184400	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 26, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31418098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002184400

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 26, 2024)

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

Novel AKAP9 mutation and long QT syndrome in a patient with torsades des pointes.

Bottigliero D, Monaco I, Santacroce R, Casavecchia G, Correale M, Guastafierro F, Leccese A, Cordisco G, Ieva R, Trunzo R, Di Biase M, Margaglione M, Brunetti ND.

J Interv Card Electrophysiol. 2019 Nov;56(2):171-172. doi: 10.1007/s10840-019-00606-y. Epub 2019 Aug 15. Review. No abstract available.

PubMed [citation]

PMID:: 31418098

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, SCV002184400.4

#	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 leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1150 of the AKAP9 protein (p.Leu1150Phe). This variant is present in population databases (rs750350575, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of long QT syndrome (PMID: 31418098). ClinVar contains an entry for this variant (Variation ID: 1412647). 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: Feb 25, 2025

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