VCV000165896.8 - ClinVar

NM_001267550.2(TTN):c.65369T>C (p.Ile21790Thr)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (3)

3 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001267550.2(TTN):c.65369T>C (p.Ile21790Thr)

Variation ID: 165896 Accession: VCV000165896.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q31.2 2: 178583813 (GRCh38) [ NCBI UCSC ] 2: 179448540 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 2, 2015	Dec 31, 2022	Sep 29, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001267550.2:c.65369T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001254479.2:p.Ile21790Thr	missense
NM_001256850.1:c.60446T>C	NP_001243779.1:p.Ile20149Thr	missense
NM_003319.4:c.38174T>C	NP_003310.4:p.Ile12725Thr	missense
NM_133378.4:c.57665T>C	NP_596869.4:p.Ile19222Thr	missense
NM_133432.3:c.38549T>C	NP_597676.3:p.Ile12850Thr	missense
NM_133437.4:c.38750T>C	NP_597681.4:p.Ile12917Thr	missense
NR_038272.1:n.2659A>G		non-coding transcript variant
NC_000002.12:g.178583813A>G
NC_000002.11:g.179448540A>G
NG_011618.3:g.251990T>C
NG_051363.1:g.65987A>G
LRG_391:g.251990T>C

... more HGVS ... less HGVS

Protein change

I19222T, I21790T, I12850T, I12917T, I12725T, I20149T

Other names

Canonical SPDI

NC_000002.12:178583812:A:G

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA178608 dbSNP: rs727503580 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
TTN		Some evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	15012	40061
TTN-AS1	-	-	-	GRCh38	-	23004

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Uncertain significance (1)	criteria provided, single submitter	Sep 26, 2013	RCV000152255.4
Autosomal recessive limb-girdle muscular dystrophy type 2J Dilated cardiomyopathy 1G	Uncertain significance (1)	criteria provided, single submitter	Nov 19, 2017	RCV000643505.4
Autosomal recessive limb-girdle muscular dystrophy type 2J Dilated cardiomyopathy 1G Early-onset myopathy with fatal cardiomyopathy Hypertrophic cardiomyopathy 9 Myopathy, myofibrillar, 9, with early respiratory failure Tibial muscular dystrophy	Uncertain significance (1)	criteria provided, single submitter	Sep 29, 2021	RCV002478435.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Nov 19, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Dilated cardiomyopathy 1G Autosomal recessive limb-girdle muscular dystrophy type 2J	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000765192.1 First in ClinVar: May 28, 2018 Last updated: May 28, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Sep 26, 2013) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000201075.5 First in ClinVar: Feb 02, 2015 Last updated: Feb 02, 2015	Comment: show The Ile19222Thr variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in larger population studies. Computational analyses (bio chemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) su ggest that this variant may not impact the normal function of the protein. Addi tional information is needed to fully assess the clinical significance of this v ariant. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 1

Uncertain significance (Sep 29, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Tibial muscular dystrophy Myopathy, myofibrillar, 9, with early respiratory failure Dilated cardiomyopathy 1G Autosomal recessive limb-girdle muscular dystrophy type 2J Early-onset myopathy with fatal cardiomyopathy Hypertrophic cardiomyopathy 9	Fulgent Genetics, Fulgent Genetics Accession: SCV002780060.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Comment:

The Ile19222Thr variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in larger population studies. Computational analyses (bio chemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) su ggest that this variant may not impact the normal function of the protein. Addi tional information is needed to fully assess the clinical significance of this v ariant.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs727503580 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 06, 2026