NM_020297.4(ABCC9):c.3594G>A (p.Met1198Ile) AND Dilated cardiomyopathy 1O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 24, 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:: RCV000465122.6

Allele description [Variation Report for NM_020297.4(ABCC9):c.3594G>A (p.Met1198Ile)]

NM_020297.4(ABCC9):c.3594G>A (p.Met1198Ile)

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.3594G>A (p.Met1198Ile)

HGVS:

NC_000012.12:g.21829033C>T
NG_012819.1:g.112662G>A
NM_001377273.1:c.3594G>A
NM_001377274.1:c.2727G>A
NM_005691.4:c.3594G>A
NM_020297.4:c.3594G>AMANE SELECT
NP_001364202.1:p.Met1198Ile
NP_001364203.1:p.Met909Ile
NP_005682.2:p.Met1198Ile
NP_005682.2:p.Met1198Ile
NP_064693.2:p.Met1198Ile
LRG_377t1:c.3594G>A
LRG_377t2:c.3594G>A
LRG_377:g.112662G>A
NC_000012.11:g.21981967C>T
NM_005691.2:c.3594G>A
NM_005691.3:c.3594G>A
NM_020297.2:c.3594G>A

Protein change:

M1198I

Links:

dbSNP: rs199900459

NCBI 1000 Genomes Browser:

rs199900459

Molecular consequence:

NM_001377273.1:c.3594G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377274.1:c.2727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005691.4:c.3594G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020297.4:c.3594G>A - 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
SCV000551687	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25979592, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000551687

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 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

Targeted 46-gene and clinical exome sequencing for mutations causing cardiomyopathies.

Waldmüller S, Schroeder C, Sturm M, Scheffold T, Imbrich K, Junker S, Frische C, Hofbeck M, Bauer P, Bonin M, Gawaz M, Gramlich M.

Mol Cell Probes. 2015 Oct;29(5):308-14. doi: 10.1016/j.mcp.2015.05.004. Epub 2015 May 12.

PubMed [citation]

PMID:: 25979592

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000551687.7

#	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 methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1198 of the ABCC9 protein (p.Met1198Ile). This variant is present in population databases (rs199900459, gnomAD 0.01%). This missense change has been observed in individual(s) with left ventricular non-compaction and Rubinstein-Taybi syndrome (PMID: 25979592). ClinVar contains an entry for this variant (Variation ID: 191584). 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 with a negative predictive value of 95%. 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: Apr 15, 2024

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