NM_020297.4(ABCC9):c.4512+814C>T AND Dilated cardiomyopathy 1O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 17, 2022
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:: RCV001852012.11

Allele description [Variation Report for NM_020297.4(ABCC9):c.4512+814C>T]

NM_020297.4(ABCC9):c.4512+814C>T

Gene:

ABCC9:ATP binding cassette subfamily C member 9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p12.1

Genomic location:

Preferred name:

NM_020297.4(ABCC9):c.4512+814C>T

HGVS:

NC_000012.12:g.21805184G>A
NG_012819.1:g.136511C>T
NM_001377273.1:c.4512+814C>T
NM_001377274.1:c.3645+814C>T
NM_005691.4:c.4640C>T
NM_020297.4:c.4512+814C>TMANE SELECT
NP_005682.2:p.Thr1547Ile
LRG_377t1:c.4512+814C>T
LRG_377t2:c.4640C>T
LRG_377:g.136511C>T
NC_000012.11:g.21958118G>A
NM_005691.2:c.4640C>T
NM_020297.2:c.4512+814C>T
O60706:p.Thr1547Ile

Protein change:

T1547I; THR1547ILE

Links:

UniProtKB: O60706#VAR_066210; OMIM: 601439.0003; dbSNP: rs387906805

NCBI 1000 Genomes Browser:

rs387906805

Molecular consequence:

NM_001377273.1:c.4512+814C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001377274.1:c.3645+814C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_020297.4:c.4512+814C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_005691.4:c.4640C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1O (CMD1O)
Synonyms:: CARDIOMYOPATHY, DILATED, WITH VENTRICULAR TACHYCARDIA
Identifiers:: MONDO: MONDO:0012062; MedGen: C1837839; Orphanet: 154; OMIM: 608569

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002179722	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17245405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002179722

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2022)

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

KATP channel mutation confers risk for vein of Marshall adrenergic atrial fibrillation.

Olson TM, Alekseev AE, Moreau C, Liu XK, Zingman LV, Miki T, Seino S, Asirvatham SJ, Jahangir A, Terzic A.

Nat Clin Pract Cardiovasc Med. 2007 Feb;4(2):110-6.

PubMed [citation]

PMID:: 17245405
PMCID:: PMC2013306

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, SCV002179722.3

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

Description

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. Experimental studies have shown that this missense change affects ABCC9 function (PMID: 17245405). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABCC9 protein function. ClinVar contains an entry for this variant (Variation ID: 30185). This missense change has been observed in individual(s) with ABCC9-related conditions (PMID: 17245405). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1547 of the ABCC9 protein (p.Thr1547Ile).

#	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: Oct 8, 2024

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