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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 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:: RCV003162339.1

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:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003906734	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Jan 31, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26112015, 31130284, 33500567 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003906734

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Jan 31, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Comprehensive gene panels provide advantages over clinical exome sequencing for Mendelian diseases.

Saudi Mendeliome Group..

Genome Biol. 2015 Jun 26;16:134. doi: 10.1186/s13059-015-0693-2. Erratum in: Genome Biol. 2015 Oct 13;16:226. doi: 10.1186/s13059-015-0798-7.

PubMed [citation]

PMID:: 26112015
PMCID:: PMC4499193

Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population.

Monies D, Abouelhoda M, Assoum M, Moghrabi N, Rafiullah R, Almontashiri N, Alowain M, Alzaidan H, Alsayed M, Subhani S, Cupler E, Faden M, Alhashem A, Qari A, Chedrawi A, Aldhalaan H, Kurdi W, Khan S, Rahbeeni Z, Alotaibi M, Goljan E, Elbardisy H, et al.

Am J Hum Genet. 2019 Jun 6;104(6):1182-1201. doi: 10.1016/j.ajhg.2019.04.011. Epub 2019 May 23. Erratum in: Am J Hum Genet. 2019 Oct 3;105(4):879. doi: 10.1016/j.ajhg.2019.09.019.

PubMed [citation]

PMID:: 31130284
PMCID:: PMC6562004

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV003906734.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Y535H variant (also known as c.1603T>C), located in coding exon 10 of the ABCC9 gene, results from a T to C substitution at nucleotide position 1603. The tyrosine at codon 535 is replaced by histidine, an amino acid with similar properties. This alteration was reported in an exome sequencing cohort, a cohort of subjects with suspected with genetic disorders and a left ventricular non-compaction (LVNC) cohort (Mazzarotto F et al. Genet Med, 2021 May;23:856-864; Monies D et al. Am J Hum Genet, 2019 Jun;104:1182-1201; Saudi Mendeliome Group. Genome Biol, 2015 Jun;16:134). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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