NM_020297.4(ABCC9):c.3283C>T (p.Arg1095Cys) AND Dilated cardiomyopathy 1O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 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:: RCV003770847.2

Allele description [Variation Report for NM_020297.4(ABCC9):c.3283C>T (p.Arg1095Cys)]

NM_020297.4(ABCC9):c.3283C>T (p.Arg1095Cys)

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.3283C>T (p.Arg1095Cys)

HGVS:

NC_000012.12:g.21844515G>A
NG_012819.1:g.97180C>T
NM_001377273.1:c.3283C>T
NM_001377274.1:c.2416C>T
NM_005691.4:c.3283C>T
NM_020297.4:c.3283C>TMANE SELECT
NP_001364202.1:p.Arg1095Cys
NP_001364203.1:p.Arg806Cys
NP_005682.2:p.Arg1095Cys
NP_064693.2:p.Arg1095Cys
LRG_377t2:c.3283C>T
LRG_377:g.97180C>T
NC_000012.11:g.21997449G>A
NM_005691.2:c.3283C>T

Protein change:

R1095C

Links:

dbSNP: rs752450127

NCBI 1000 Genomes Browser:

rs752450127

Molecular consequence:

NM_001377273.1:c.3283C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001377274.1:c.2416C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005691.4:c.3283C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_020297.4:c.3283C>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
SCV004669335	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 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

SCV004669335

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 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, SCV004669335.1

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

Description

This variant has not been reported in the literature in individuals affected with ABCC9-related conditions. This variant is present in population databases (rs752450127, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1095 of the ABCC9 protein (p.Arg1095Cys). ClinVar contains an entry for this variant (Variation ID: 1030958). 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 expected to disrupt ABCC9 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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