VCV000535377.6 - ClinVar

NM_001267550.2(TTN):c.62816G>A (p.Arg20939His)

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.62816G>A (p.Arg20939His)

Variation ID: 535377 Accession: VCV000535377.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q31.2 2: 178588909 (GRCh38) [ NCBI UCSC ] 2: 179453636 (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	May 28, 2018	May 1, 2024	Nov 11, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001267550.2:c.62816G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001254479.2:p.Arg20939His	missense
NM_001256850.1:c.57893G>A	NP_001243779.1:p.Arg19298His	missense
NM_003319.4:c.35621G>A	NP_003310.4:p.Arg11874His	missense
NM_133378.4:c.55112G>A	NP_596869.4:p.Arg18371His	missense
NM_133432.3:c.35996G>A	NP_597676.3:p.Arg11999His	missense
NM_133437.4:c.36197G>A	NP_597681.4:p.Arg12066His	missense
NC_000002.12:g.178588909C>T
NC_000002.11:g.179453636C>T
NG_011618.3:g.246894G>A
NG_051363.1:g.71083C>T
LRG_391:g.246894G>A

... more HGVS ... less HGVS

Protein change

R20939H, R11874H, R19298H, R11999H, R12066H, R18371H

Other names

Canonical SPDI

NC_000002.12:178588908:C:T

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), exomes 0.00002

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Exome Aggregation Consortium (ExAC) 0.00003

The Genome Aggregation Database (gnomAD) 0.00003

The Genome Aggregation Database (gnomAD) 0.00004

Links

ClinGen: CA1992179 dbSNP: rs777095470 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	14949	39877
TTN-AS1	-	-	-	GRCh38	-	22894

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	Oct 26, 2017	RCV000643318.4
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	Sep 24, 2019	RCV002334125.2
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	Nov 11, 2021	RCV002483844.1

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 (Oct 26, 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: SCV000765005.1 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 (Nov 11, 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: SCV002787121.1 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

Uncertain significance (Sep 24, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002618841.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: show The p.R11874H variant (also known as c.35621G>A), located in coding exon 131 of the TTN gene, results from a G to A substitution at nucleotide position 35621. The arginine at codon 11874 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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 p.R11874H variant (also known as c.35621G>A), located in coding exon 131 of the TTN gene, results from a G to A substitution at nucleotide position 35621. The arginine at codon 11874 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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 rs777095470 ...

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