NM_001267550.2(TTN):c.54649A>G (p.Ser18217Gly) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 14, 2024
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:: RCV003139936.4

Allele description [Variation Report for NM_001267550.2(TTN):c.54649A>G (p.Ser18217Gly)]

NM_001267550.2(TTN):c.54649A>G (p.Ser18217Gly)

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.54649A>G (p.Ser18217Gly)

HGVS:

NC_000002.12:g.178604038T>C
NG_011618.3:g.231765A>G
NG_051363.1:g.86212T>C
NM_001256850.1:c.49726A>G
NM_001267550.2:c.54649A>GMANE SELECT
NM_003319.4:c.27454A>G
NM_133378.4:c.46945A>G
NM_133432.3:c.27829A>G
NM_133437.4:c.28030A>G
NP_001243779.1:p.Ser16576Gly
NP_001254479.2:p.Ser18217Gly
NP_003310.4:p.Ser9152Gly
NP_596869.4:p.Ser15649Gly
NP_597676.3:p.Ser9277Gly
NP_597681.4:p.Ser9344Gly
LRG_391:g.231765A>G
NC_000002.11:g.179468765T>C
NM_001267550.2:c.54649A>G
NM_133378.4:c.46945A>G

Protein change:

S15649G

Links:

dbSNP: rs201001270

NCBI 1000 Genomes Browser:

rs201001270

Molecular consequence:

NM_001256850.1:c.49726A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.54649A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.27454A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.46945A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.27829A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.28030A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003818488	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005879276	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	Uncertain Significance (May 14, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003818488

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 17, 2021)

germline

clinical testing

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

SCV005879276

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process 2024)

Uncertain Significance
(May 14, 2024)

germline

clinical testing

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

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 Revvity Omics, Revvity, SCV003818488.2

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV005879276.1

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

Description

The TTN c.54649A>G; p.Ser18217Gly variant (rs201001270; ClinVar Variation ID: 518573) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Ser18217Gly variant cannot be determined with certainty.

#	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: May 16, 2025

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