NM_020297.4(ABCC9):c.1603T>C (p.Tyr535His) AND Dilated cardiomyopathy 1O

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 11, 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:: RCV000792599.9

Allele description [Variation Report for NM_020297.4(ABCC9):c.1603T>C (p.Tyr535His)]

NM_020297.4(ABCC9):c.1603T>C (p.Tyr535His)

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.1603T>C (p.Tyr535His)

HGVS:

NC_000012.12:g.21906141A>G
NG_012819.1:g.35554T>C
NM_001377273.1:c.1603T>C
NM_001377274.1:c.739T>C
NM_005691.4:c.1603T>C
NM_020297.4:c.1603T>CMANE SELECT
NP_001364202.1:p.Tyr535His
NP_001364203.1:p.Tyr247His
NP_005682.2:p.Tyr535His
NP_005682.2:p.Tyr535His
NP_064693.2:p.Tyr535His
LRG_377t1:c.1603T>C
LRG_377t2:c.1603T>C
LRG_377:g.35554T>C
NC_000012.11:g.22059075A>G
NM_005691.2:c.1603T>C
NM_005691.3:c.1603T>C
NM_020297.2:c.1603T>C
c.1603T>C

Protein change:

Y247H

Links:

dbSNP: rs397517184

NCBI 1000 Genomes Browser:

rs397517184

Molecular consequence:

NM_001377273.1:c.1603T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001377274.1:c.739T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005691.4:c.1603T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_020297.4:c.1603T>C - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000931905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33500567, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000931905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 11, 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

Systematic large-scale assessment of the genetic architecture of left ventricular noncompaction reveals diverse etiologies.

Mazzarotto F, Hawley MH, Beltrami M, Beekman L, de Marvao A, McGurk KA, Statton B, Boschi B, Girolami F, Roberts AM, Lodder EM, Allouba M, Romeih S, Aguib Y, Baksi AJ, Pantazis A, Prasad SK, Cerbai E, Yacoub MH, O'Regan DP, Cook SA, Ware JS, et al.

Genet Med. 2021 May;23(5):856-864. doi: 10.1038/s41436-020-01049-x. Epub 2021 Jan 26.

PubMed [citation]

PMID:: 33500567
PMCID:: PMC8105165

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, SCV000931905.6

#	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 45389). This missense change has been observed in individual(s) with left ventricular noncompaction (PMID: 33500567). This variant is present in population databases (rs397517184, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 535 of the ABCC9 protein (p.Tyr535His).

#	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

ClinVar

Relating variation to medicine