VCV000281477.14 - ClinVar

NM_001267550.2(TTN):c.107450C>T (p.Ser35817Leu)

Germline

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.

(7)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(4); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001267550.2(TTN):c.107450C>T (p.Ser35817Leu)

Variation ID: 281477 Accession: VCV000281477.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q31.2 2: 178527676 (GRCh38) [ NCBI UCSC ] 2: 179392403 (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	Apr 3, 2017	May 1, 2024	Oct 17, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001267550.2:c.107450C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001254479.2:p.Ser35817Leu	missense
NM_001256850.1:c.102527C>T	NP_001243779.1:p.Ser34176Leu	missense
NM_003319.4:c.80255C>T	NP_003310.4:p.Ser26752Leu	missense
NM_133378.4:c.99746C>T	NP_596869.4:p.Ser33249Leu	missense
NM_133432.3:c.80630C>T	NP_597676.3:p.Ser26877Leu	missense
NM_133437.4:c.80831C>T	NP_597681.4:p.Ser26944Leu	missense
NC_000002.12:g.178527676G>A
NC_000002.11:g.179392403G>A
NG_011618.3:g.308127C>T
NG_051363.1:g.9850G>A
LRG_391:g.308127C>T

... more HGVS ... less HGVS

Protein change

S35817L, S33249L, S34176L, S26752L, S26877L, S26944L

Other names

Canonical SPDI

NC_000002.12:178527675:G:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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

Links

ClinGen: CA1984935 dbSNP: rs766440492 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	12026	32050
TTN-AS1	-	-	-	GRCh38	-	18375

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 provided	Uncertain significance (4)	criteria provided, multiple submitters, no conflicts	Aug 20, 2019	RCV000337417.11
Cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Feb 14, 2017	RCV000769837.2
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	Oct 17, 2021	RCV002487185.1
Cardiovascular phenotype	Likely benign (1)	criteria provided, single submitter	May 14, 2020	RCV002411146.2

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.	More information 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 (Jan 26, 2016)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000338500.3 First in ClinVar: Dec 06, 2016 Last updated: Apr 03, 2017	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN Number of individuals with the variant: 1 Sex: mixed
Uncertain significance (Feb 14, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Study: Canadian Open Genetics Repository Accession: SCV000901263.1 First in ClinVar: May 06, 2019 Last updated: May 06, 2019
Uncertain significance (Oct 17, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	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 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002786873.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Aug 20, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003819622.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Likely benign (May 14, 2020)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002675961.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Uncertain significance (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001978973.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021
Uncertain significance (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001979501.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TTN	-	-	-	-

Text-mined citations for rs766440492 ...

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 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001267550.2(TTN):c.107450C>T (p.Ser35817Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs766440492 ...