NM_020297.4(ABCC9):c.2857G>A (p.Glu953Lys) AND Dilated cardiomyopathy 1O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 22, 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:: RCV000640326.5

Allele description [Variation Report for NM_020297.4(ABCC9):c.2857G>A (p.Glu953Lys)]

NM_020297.4(ABCC9):c.2857G>A (p.Glu953Lys)

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.2857G>A (p.Glu953Lys)

HGVS:

NC_000012.12:g.21848159C>T
NG_012819.1:g.93536G>A
NM_001377273.1:c.2857G>A
NM_001377274.1:c.1990G>A
NM_005691.4:c.2857G>A
NM_020297.2:c.2857G>A
NM_020297.4:c.2857G>AMANE SELECT
NP_001364202.1:p.Glu953Lys
NP_001364203.1:p.Glu664Lys
NP_005682.2:p.Glu953Lys
NP_005682.2:p.Glu953Lys
NP_064693.2:p.Glu953Lys
LRG_377t1:c.2857G>A
LRG_377t2:c.2857G>A
LRG_377:g.93536G>A
NC_000012.11:g.22001093C>T
NM_005691.2:c.2857G>A
NM_005691.3:c.2857G>A

Protein change:

E664K

Links:

dbSNP: rs143685061

NCBI 1000 Genomes Browser:

rs143685061

Molecular consequence:

NM_001377273.1:c.2857G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001377274.1:c.1990G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005691.4:c.2857G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020297.4:c.2857G>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

Recent activity

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PREDICTED: Homo sapiens small nucleolar RNA SNORA22 (LOC124900327), ncRNA
PREDICTED: Homo sapiens small nucleolar RNA SNORA22 (LOC124900327), ncRNA
gi|2217478866|ref|XR_007083496.1|

Nucleotide
F-box associated ubiquitination effector family protein [Arabidopsis thaliana]
F-box associated ubiquitination effector family protein [Arabidopsis thaliana]
gi|15224566|ref|NP_178628.1|

Protein
Homo sapiens minichromosome maintenance domain containing 2 (MCMDC2), transcript...
Homo sapiens minichromosome maintenance domain containing 2 (MCMDC2), transcript variant 1, mRNA
gi|1519311606|ref|NM_173518.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761915	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000761915

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 22, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV000761915.4

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

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 953 of the ABCC9 protein (p.Glu953Lys). This variant is present in population databases (rs143685061, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. ClinVar contains an entry for this variant (Variation ID: 533282). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCC9 protein function. 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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Relating variation to medicine