NM_001267550.2(TTN):c.67318G>A (p.Gly22440Ser) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 11, 2019
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:: RCV002354351.2

Allele description [Variation Report for NM_001267550.2(TTN):c.67318G>A (p.Gly22440Ser)]

NM_001267550.2(TTN):c.67318G>A (p.Gly22440Ser)

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.67318G>A (p.Gly22440Ser)

HGVS:

NC_000002.12:g.178579969C>T
NG_011618.3:g.255834G>A
NG_051363.1:g.62143C>T
NM_001256850.1:c.62395G>A
NM_001267550.2:c.67318G>AMANE SELECT
NM_003319.4:c.40123G>A
NM_133378.4:c.59614G>A
NM_133432.3:c.40498G>A
NM_133437.4:c.40699G>A
NP_001243779.1:p.Gly20799Ser
NP_001254479.2:p.Gly22440Ser
NP_003310.4:p.Gly13375Ser
NP_596869.4:p.Gly19872Ser
NP_597676.3:p.Gly13500Ser
NP_597681.4:p.Gly13567Ser
LRG_391:g.255834G>A
NC_000002.11:g.179444696C>T
NM_001267550.2:c.67318G>A
NM_003319.4:c.40123G>A

Protein change:

G13375S

Links:

dbSNP: rs727503576

NCBI 1000 Genomes Browser:

rs727503576

Molecular consequence:

NM_001256850.1:c.62395G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.67318G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.40123G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.59614G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.40498G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.40699G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002621128	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jul 11, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002621128

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jul 11, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Citations

PubMed

Hypertrophy Regression With N-Acetylcysteine in Hypertrophic Cardiomyopathy (HALT-HCM): A Randomized, Placebo-Controlled, Double-Blind Pilot Study.

Marian AJ, Tan Y, Li L, Chang J, Syrris P, Hessabi M, Rahbar MH, Willerson JT, Cheong BY, Liu CY, Kleiman NS, Bluemke DA, Nagueh SF.

Circ Res. 2018 Apr 13;122(8):1109-1118. doi: 10.1161/CIRCRESAHA.117.312647. Epub 2018 Mar 14.

PubMed [citation]

PMID:: 29540445
PMCID:: PMC5899034

Details of each submission

From Ambry Genetics, SCV002621128.2

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

Description

The p.G13375S variant (also known as c.40123G>A), located in coding exon 145 of the TTN gene, results from a G to A substitution at nucleotide position 40123. The glycine at codon 13375 is replaced by serine, an amino acid with similar properties. This variant (reported as p.G22440S, c.67318G>A) has been detected in a hypertrophic cardiomyopathy cohort; however, details were limited (Marian AJ et al. Circ. Res., 2018 Apr;122:1109-1118). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 16, 2025

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