NM_001267550.2(TTN):c.104377A>C (p.Met34793Leu) AND not specified

Germline classification:: Benign/Likely benign (7 submissions)
Last evaluated:: Aug 24, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000040939.22

Allele description [Variation Report for NM_001267550.2(TTN):c.104377A>C (p.Met34793Leu)]

NM_001267550.2(TTN):c.104377A>C (p.Met34793Leu)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.104377A>C (p.Met34793Leu)

Other names:

p.M33152L:ATG>CTG

HGVS:

NC_000002.12:g.178532238T>G
NG_011618.3:g.303565A>C
NG_051363.1:g.14412T>G
NM_001256850.1:c.99454A>C
NM_001267550.2:c.104377A>CMANE SELECT
NM_003319.4:c.77182A>C
NM_133378.4:c.96673A>C
NM_133432.3:c.77557A>C
NM_133437.4:c.77758A>C
NP_001243779.1:p.Met33152Leu
NP_001254479.1:p.Met34793Leu
NP_001254479.2:p.Met34793Leu
NP_003310.4:p.Met25728Leu
NP_596869.4:p.Met32225Leu
NP_597676.3:p.Met25853Leu
NP_597681.4:p.Met25920Leu
LRG_391t1:c.104377A>C
LRG_391:g.303565A>C
LRG_391p1:p.Met34793Leu
NC_000002.11:g.179396965T>G
NM_001267550.1:c.104377A>C
NM_133379.3:c.*213347A>C
c.96673A>C

Protein change:

M25728L

Links:

dbSNP: rs72629787

NCBI 1000 Genomes Browser:

rs72629787

Molecular consequence:

NM_001256850.1:c.99454A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.104377A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.77182A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.96673A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.77557A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.77758A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051712	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000064630	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Apr 10, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000169469	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Mar 27, 2014)	germline	clinical testing	Citation Link,
SCV001431966	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Aug 24, 2020)	germline	clinical testing	Citation Link,
SCV001477102	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Feb 18, 2020)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23861362, 26467025
SCV001918432	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001958245	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	Benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	4	not provided	not provided	not provided	not provided	clinical testing, research
not provided	germline	not provided	19	19	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

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

See all PubMed Citations (3)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000051712.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	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		4	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000064630.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	19	not provided	not provided	clinical testing	PubMed (1)

Description

2.6% (82/3172) of Afr American chrom in ESP

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		19	not provided	19	not provided

From GeneDx, SCV000169469.11

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

Description

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.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001431966.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV001477102.1

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

#	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		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001918432.1

#	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, SCV001958245.1

#	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: Nov 3, 2024

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