NM_001267550.2(TTN):c.99946G>A (p.Ala33316Thr) AND not specified

Germline classification:: Benign (1 submission)
Last evaluated:: Mar 11, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004525889.1

Allele description [Variation Report for NM_001267550.2(TTN):c.99946G>A (p.Ala33316Thr)]

NM_001267550.2(TTN):c.99946G>A (p.Ala33316Thr)

Genes:

LOC126806420:BRD4-independent group 4 enhancer GRCh37_chr2:179401104-179402303 [Gene]
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.99946G>A (p.Ala33316Thr)

Other names:

p.A31675T:GCA>ACA

HGVS:

NC_000002.12:g.178537163C>T
NG_011618.3:g.298640G>A
NG_051363.1:g.19337C>T
NM_001256850.1:c.95023G>A
NM_001267550.2:c.99946G>AMANE SELECT
NM_003319.4:c.72751G>A
NM_133378.4:c.92242G>A
NM_133432.3:c.73126G>A
NM_133437.4:c.73327G>A
NP_001243779.1:p.Ala31675Thr
NP_001254479.2:p.Ala33316Thr
NP_003310.4:p.Ala24251Thr
NP_596869.4:p.Ala30748Thr
NP_597676.3:p.Ala24376Thr
NP_597681.4:p.Ala24443Thr
LRG_391:g.298640G>A
NC_000002.11:g.179401890C>T
NM_003319.4:c.72751G>A
NM_133378.4:c.92242G>A

Protein change:

A24251T

Links:

dbSNP: rs374295768

NCBI 1000 Genomes Browser:

rs374295768

Molecular consequence:

NM_001256850.1:c.95023G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.99946G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.72751G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.92242G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.73126G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.73327G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV005039499	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 11, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005039499

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 11, 2024)

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	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005039499.1

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

Description

Variant summary: TTN c.92242G>A (p.Ala30748Thr) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 1606638 control chromosomes, predominantly at a frequency of 0.001 within the South Asian subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2.56 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.92242G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 203051). Based on the evidence outlined above, the variant was classified as likely benign.

#	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: Jun 17, 2024

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