NM_001267550.2(TTN):c.22628C>T (p.Pro7543Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 13, 2025
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:: RCV005418206.1

Allele description [Variation Report for NM_001267550.2(TTN):c.22628C>T (p.Pro7543Leu)]

NM_001267550.2(TTN):c.22628C>T (p.Pro7543Leu)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.22628C>T (p.Pro7543Leu)

HGVS:

NC_000002.12:g.178722035G>A
NG_011618.3:g.113768C>T
NM_001256850.1:c.21677C>T
NM_001267550.2:c.22628C>TMANE SELECT
NM_003319.4:c.13282+16047C>T
NM_133378.4:c.18896C>T
NM_133432.3:c.13657+16047C>T
NM_133437.4:c.13858+16047C>T
NP_001243779.1:p.Pro7226Leu
NP_001254479.2:p.Pro7543Leu
NP_596869.4:p.Pro6299Leu
LRG_391:g.113768C>T
NC_000002.11:g.179586762G>A
NM_133378.4:c.18896C>T

Protein change:

P6299L

Links:

dbSNP: rs560272834

NCBI 1000 Genomes Browser:

rs560272834

Molecular consequence:

NM_003319.4:c.13282+16047C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+16047C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+16047C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.21677C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.22628C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.18896C>T - 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
SCV006086585	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 13, 2025)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV006086585

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 13, 2025)

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, SCV006086585.1

#	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.18896C>T (p.Pro6299Leu) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 0.0001 in 248626 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Autosomal Recessive Titinopathy (0.0001 vs 0.00039), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.18896C>T in individuals affected with Autosomal Recessive Titinopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 466908). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Sep 6, 2025

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