NM_001267550.2(TTN):c.24964G>T (p.Val8322Leu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (9 submissions)
Last evaluated:: Jan 1, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000172688.33

Allele description [Variation Report for NM_001267550.2(TTN):c.24964G>T (p.Val8322Leu)]

NM_001267550.2(TTN):c.24964G>T (p.Val8322Leu)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.24964G>T (p.Val8322Leu)

Other names:

p.V7078L:GTA>TTA

HGVS:

NC_000002.12:g.178718042C>A
NG_011618.3:g.117761G>T
NM_001256850.1:c.24013G>T
NM_001267550.2:c.24964G>TMANE SELECT
NM_003319.4:c.13282+20040G>T
NM_133378.4:c.21232G>T
NM_133432.3:c.13657+20040G>T
NM_133437.4:c.13858+20040G>T
NP_001243779.1:p.Val8005Leu
NP_001254479.2:p.Val8322Leu
NP_596869.4:p.Val7078Leu
LRG_391t1:c.24964G>T
LRG_391:g.117761G>T
NC_000002.11:g.179582769C>A
NM_001267550.1:c.24964G>T

Protein change:

V7078L

Links:

dbSNP: rs201571580

NCBI 1000 Genomes Browser:

rs201571580

Molecular consequence:

NM_003319.4:c.13282+20040G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+20040G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+20040G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.24013G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.24964G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.21232G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051302	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Likely benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000238355	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (May 26, 2021)	germline	clinical testing	Citation Link,
SCV000701175	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Nov 21, 2017)	germline	clinical testing	Citation Link,
SCV000844655	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely benign (Feb 9, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001153030	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jan 1, 2024)	germline	clinical testing	Citation Link,
SCV001157863	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Likely benign (Feb 28, 2022)	germline	clinical testing	Citation Link,
SCV001800244	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001957324	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing
SCV001971446	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	2	not provided	not provided	not provided	not provided	research
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	7	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000051302.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV000238355.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000701175.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		7	not provided	not provided	not provided

From Athena Diagnostics Inc, SCV000844655.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV001153030.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

TTN: BP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001157863.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV001800244.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001957324.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001971446.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

Relating variation to medicine