VCV000467082.6 - ClinVar

NM_001267550.2(TTN):c.37502C>T (p.Pro12501Leu)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(3); Likely benign(1)

4 out of 4 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.37502C>T (p.Pro12501Leu)

Variation ID: 467082 Accession: VCV000467082.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q31.2 2: 178658746 (GRCh38) [ NCBI UCSC ] 2: 179523473 (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	Dec 26, 2017	Nov 20, 2023	Oct 9, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001267550.2:c.37502C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001254479.2:p.Pro12501Leu	missense
NM_001256850.1:c.34522+259C>T		intron variant
NM_003319.4:c.13283-16429C>T		intron variant
NM_133378.4:c.31741+259C>T		intron variant
NM_133432.3:c.13658-16429C>T		intron variant
NM_133437.4:c.13859-16429C>T		intron variant
NC_000002.12:g.178658746G>A
NC_000002.11:g.179523473G>A
NG_011618.3:g.177057C>T
LRG_391:g.177057C>T
LRG_391t1:c.37502C>T

... more HGVS ... less HGVS

Protein change

P12501L

Other names

Canonical SPDI

NC_000002.12:178658745:G:A

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.

The Genome Aggregation Database (gnomAD) 0.00010

Links

ClinGen: CA349484155 dbSNP: rs1236045684 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		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	14006	37498

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.
Autosomal recessive limb-girdle muscular dystrophy type 2J Dilated cardiomyopathy 1G	Uncertain significance (1)	criteria provided, single submitter	May 16, 2017	RCV000549749.4
not provided	Uncertain significance (1)	criteria provided, single submitter	Apr 18, 2018	RCV000714021.2
Primary dilated cardiomyopathy	Likely benign (1)	criteria provided, single submitter	-	RCV001293184.1
TTN-related disorder	Uncertain significance (1)	criteria provided, single submitter	Oct 9, 2023	RCV004537984.1

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 (May 16, 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: SCV000643072.1 First in ClinVar: Dec 26, 2017 Last updated: Dec 26, 2017	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 (Apr 18, 2018) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria)	not provided	Athena Diagnostics Accession: SCV000844684.1 First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 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

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Primary dilated cardiomyopathy	Genetics and Genomics Program, Sidra Medicine Accession: SCV001434182.1 First in ClinVar: Feb 28, 2021 Last updated: Feb 28, 2021	Observation: 1 Collection method: research Allele origin: unknown Affected status: yes more Observation 1 Collection method: research Allele origin: unknown Affected status: yes Number of individuals with the variant: 1 Test name: Trusight Cardio Sequencing Platform type: next-gen sequencing

Uncertain significance (Oct 09, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	TTN-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004120426.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: show The TTN c.37502C>T variant is predicted to result in the amino acid substitution p.Pro12501Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179523473-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The TTN c.37502C>T variant is predicted to result in the amino acid substitution p.Pro12501Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.035% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179523473-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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 rs1236045684 ...

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 May 17, 2025