NM_001267550.2(TTN):c.82754C>A (p.Ser27585Tyr) AND not specified

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Apr 9, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000222951.9

Allele description [Variation Report for NM_001267550.2(TTN):c.82754C>A (p.Ser27585Tyr)]

NM_001267550.2(TTN):c.82754C>A (p.Ser27585Tyr)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.82754C>A (p.Ser27585Tyr)

Other names:

p.S25017Y:TCT>TAT

HGVS:

NC_000002.12:g.178563378G>T
NG_011618.3:g.272425C>A
NG_051363.1:g.45552G>T
NM_001256850.1:c.77831C>A
NM_001267550.2:c.82754C>AMANE SELECT
NM_003319.4:c.55559C>A
NM_133378.4:c.75050C>A
NM_133432.3:c.55934C>A
NM_133437.4:c.56135C>A
NP_001243779.1:p.Ser25944Tyr
NP_001254479.2:p.Ser27585Tyr
NP_003310.4:p.Ser18520Tyr
NP_596869.4:p.Ser25017Tyr
NP_597676.3:p.Ser18645Tyr
NP_597681.4:p.Ser18712Tyr
LRG_391:g.272425C>A
NC_000002.11:g.179428105G>T

Protein change:

S18520Y

Links:

dbSNP: rs72648215

NCBI 1000 Genomes Browser:

rs72648215

Molecular consequence:

NM_001256850.1:c.77831C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.82754C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.55559C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.75050C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.55934C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.56135C>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
SCV000272774	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Dec 18, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV006069988	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 9, 2025)	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

SCV000272774

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Dec 18, 2014)

germline

clinical testing

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

SCV006069988

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Apr 9, 2025)

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	1	1	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000272774.3

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

Description

The p.Ser25017Tyr variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 11/67626 European chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs72648215). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Ser25017Tyr variant is uncertain.

#	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		1	not provided	1	not provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV006069988.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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