NM_001267550.2(TTN):c.28507G>A (p.Val9503Ile) AND not specified

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Nov 17, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000152385.8

Allele description [Variation Report for NM_001267550.2(TTN):c.28507G>A (p.Val9503Ile)]

NM_001267550.2(TTN):c.28507G>A (p.Val9503Ile)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.28507G>A (p.Val9503Ile)

Other names:

p.V9186I:GTA>ATA

HGVS:

NC_000002.12:g.178709812C>T
NG_011618.3:g.125991G>A
NM_001256850.1:c.27556G>A
NM_001267550.2:c.28507G>AMANE SELECT
NM_003319.4:c.13282+28270G>A
NM_133378.4:c.24775G>A
NM_133432.3:c.13657+28270G>A
NM_133437.4:c.13858+28270G>A
NP_001243779.1:p.Val9186Ile
NP_001254479.2:p.Val9503Ile
NP_596869.4:p.Val8259Ile
LRG_391t1:c.28507G>A
LRG_391:g.125991G>A
NC_000002.11:g.179574539C>T
NM_001267550.1:c.28507G>A

Protein change:

V8259I

Links:

dbSNP: rs202160275

NCBI 1000 Genomes Browser:

rs202160275

Molecular consequence:

NM_003319.4:c.13282+28270G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+28270G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+28270G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.27556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.28507G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.24775G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000201353	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Jul 16, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000616046	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely benign (Nov 17, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23861362, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000201353

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely benign
(Jul 16, 2014)

germline

clinical testing

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

SCV000616046

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely benign
(Nov 17, 2016)

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
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program.

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000201353.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

Description

Val8259Ile in exon 96 of TTN: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, squirrel, rat, shrew, aardvark and multiple lower species have an isoleucine (Ile) at this position despite high nearby amino acid conservation. It has also been identified in 2/8158 European American chromosomes by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs202160275).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

From Athena Diagnostics, SCV000616046.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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: Mar 11, 2025

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