VCV000179179.27 - ClinVar

NM_001267550.2(TTN):c.18075C>T (p.Pro6025=)

Germline

Classification

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

Benign/Likely benign
Benign (6); Likely benign (3)

9 out of 12 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.18075C>T (p.Pro6025=)

Variation ID: 179179 Accession: VCV000179179.27

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q31.2 2: 179595052 (GRCh37) [ NCBI UCSC ] 2: 178730325 (GRCh38) [ 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	Apr 9, 2018	Oct 3, 2026	Feb 2, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001267550.2:c.18075C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001254479.2:p.Pro6025=	synonymous
NM_001256850.1:c.17124C>T	NP_001243779.1:p.Pro5708=	synonymous
NM_003319.4:c.13282+7757C>T		intron variant
NM_133378.4:c.14343C>T	NP_596869.4:p.Pro4781=	synonymous
NM_133432.3:c.13657+7757C>T		intron variant
NM_133437.4:c.13858+7757C>T		intron variant
NC_000002.12:g.178730325G>A
NC_000002.11:g.179595052G>A
NG_011618.3:g.105478C>T
LRG_391:g.105478C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000002.12:178730324: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.

0.00160 (A)

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

Exome Aggregation Consortium (ExAC) 0.00064

1000 Genomes Project 30x 0.00141

1000 Genomes Project 0.00160

The Genome Aggregation Database (gnomAD) 0.00000

Trans-Omics for Precision Medicine (TOPMed) 0.00005

The Genome Aggregation Database (gnomAD) 0.00017

The Genome Aggregation Database (gnomAD), exomes 0.00025

Links

ClinGen: CA183882 dbSNP: rs557350005 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	15677	41444

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	Likely benign (3)	criteria provided, multiple submitters, no conflicts	Dec 13, 2017	RCV000155965.7
Autosomal recessive limb-girdle muscular dystrophy type 2J Dilated cardiomyopathy 1G	Benign (1)	criteria provided, single submitter	Feb 2, 2026	RCV000539068.13
Cardiomyopathy	Benign (1)	criteria provided, single submitter	Oct 30, 2017	RCV000769073.2
not provided	Likely benign (2)	no assertion criteria provided	-	RCV001529672.3
Autosomal recessive limb-girdle muscular dystrophy type 2J	Benign (1)	criteria provided, single submitter	Sep 10, 2021	RCV001840172.2
Early-onset myopathy with fatal cardiomyopathy	Benign (1)	criteria provided, single submitter	Sep 10, 2021	RCV001840174.2
Tibial muscular dystrophy	Benign (1)	criteria provided, single submitter	Sep 10, 2021	RCV001840171.2
Myopathy, myofibrillar, 9, with early respiratory failure	Benign (1)	criteria provided, single submitter	Sep 10, 2021	RCV001840173.2
TTN-related disorder	Likely benign (1)	criteria provided, single submitter	Feb 2, 2026	RCV006989137.1

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.
Likely benign (Dec 13, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000725805.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Oct 30, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Study: Canadian Open Genetics Repository Accession: SCV000900446.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Sep 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Autosomal recessive limb-girdle muscular dystrophy type 2J	Genome-Nilou Lab Accession: SCV002099994.1 First in ClinVar: Mar 04, 2022 Last updated: Mar 04, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Sep 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Myopathy, myofibrillar, 9, with early respiratory failure	Genome-Nilou Lab Accession: SCV002099995.1 First in ClinVar: Mar 04, 2022 Last updated: Mar 04, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Sep 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Early-onset myopathy with fatal cardiomyopathy	Genome-Nilou Lab Accession: SCV002099996.1 First in ClinVar: Mar 04, 2022 Last updated: Mar 04, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Sep 10, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Tibial muscular dystrophy	Genome-Nilou Lab Accession: SCV002099997.1 First in ClinVar: Mar 04, 2022 Last updated: Mar 04, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely benign (Feb 02, 2026) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	TTN-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV007989531.1 First in ClinVar: Oct 03, 2026 Last updated: Oct 03, 2026	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (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

Likely benign (Sep 13, 2013) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000205677.5 First in ClinVar: Jan 31, 2015 Last updated: Apr 09, 2018	Comment: show Pro4781Pro in exon 59 of TTN: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Pro4781Pro in exon 59 of TTN (allele frequenc y = n/a) (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: 2

Benign (Feb 02, 2026) 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 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000642747.10 First in ClinVar: Dec 26, 2017 Last updated: Feb 23, 2026	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 (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001743516.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified	Clinical Genetics, Academic Medical Center Study: VKGL Data-share Consensus Accession: SCV001918966.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV001972248.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

Pro4781Pro in exon 59 of TTN: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Pro4781Pro in exon 59 of TTN (allele frequenc y = n/a)

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 rs557350005 ...

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 Oct 04, 2026