NM_001267550.2(TTN):c.106675G>C (p.Glu35559Gln) AND not specified

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Sep 22, 2021
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:: RCV000222652.14

Allele description [Variation Report for NM_001267550.2(TTN):c.106675G>C (p.Glu35559Gln)]

NM_001267550.2(TTN):c.106675G>C (p.Glu35559Gln)

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.106675G>C (p.Glu35559Gln)

Other names:

p.E33918Q:GAA>CAA

HGVS:

NC_000002.12:g.178529076C>G
NG_011618.3:g.306727G>C
NG_051363.1:g.11250C>G
NM_001256850.1:c.101752G>C
NM_001267550.2:c.106675G>CMANE SELECT
NM_003319.4:c.79480G>C
NM_133378.4:c.98971G>C
NM_133432.3:c.79855G>C
NM_133437.4:c.80056G>C
NP_001243779.1:p.Glu33918Gln
NP_001254479.2:p.Glu35559Gln
NP_003310.4:p.Glu26494Gln
NP_596869.4:p.Glu32991Gln
NP_597676.3:p.Glu26619Gln
NP_597681.4:p.Glu26686Gln
LRG_391t1:c.106675G>C
LRG_391:g.306727G>C
NC_000002.11:g.179393803C>G
NM_001267550.1:c.106675G>C

Protein change:

E26494Q

Links:

dbSNP: rs199632397

NCBI 1000 Genomes Browser:

rs199632397

Molecular consequence:

NM_001256850.1:c.101752G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.106675G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.79480G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.98971G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.79855G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.80056G>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
SCV000272837	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jul 10, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27930701, 24033266
SCV000334023	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Sep 1, 2015)	germline	clinical testing	Citation Link,
SCV001983690	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Sep 22, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000272837

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jul 10, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000334023

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Likely benign
(Sep 1, 2015)

germline

clinical testing

Citation Link,

SCV001983690

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Sep 22, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Natural and Undetermined Sudden Death: Value of Post-Mortem Genetic Investigation.

Sanchez O, Campuzano O, Fernández-Falgueras A, Sarquella-Brugada G, Cesar S, Mademont I, Mates J, Pérez-Serra A, Coll M, Pico F, Iglesias A, Tirón C, Allegue C, Carro E, Gallego MÁ, Ferrer-Costa C, Hospital A, Bardalet N, Borondo JC, Vingut A, Arbelo E, Brugada J, et al.

PLoS One. 2016;11(12):e0167358. doi: 10.1371/journal.pone.0167358. Erratum in: PLoS One. 2017 Feb 6;12 (2):e0171893.

PubMed [citation]

PMID:: 27930701
PMCID:: PMC5145162

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

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000272837.3

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

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Glu32991Gln v ariant has been identified by our laboratory in 1 Caucasian individual with idio pathic cardiomyopathy and in 0.1% (34/30728) of South Asian chromosomes by the G enome Aggreagation Database (gnomAD, http://gnomad.broadinstitute.org/, dbSNP rs 199632397). This variant was also identified in a 23-year-old female who died su ddenly; however, the specific cause of her death was unexplained even after auto psy (Sanchez 2016). This variant has also been reported in ClinVar (Variation ID 192135). Computational prediction tools and conservation analysis suggest that the p.Glu32991Gln variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Glu32991Gln variant is uncertain, its frequency suggests that it is more likely to be benign.

#	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		2	not provided	2	not provided

From Eurofins Ntd Llc (ga), SCV000334023.4

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983690.1

#	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

Last Updated: Apr 15, 2024

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