NM_001267550.2(TTN):c.95195C>T (p.Pro31732Leu) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 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:: RCV000684823.10

Allele description [Variation Report for NM_001267550.2(TTN):c.95195C>T (p.Pro31732Leu)]

NM_001267550.2(TTN):c.95195C>T (p.Pro31732Leu)

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.95195C>T (p.Pro31732Leu)

Other names:

Q8WZ42.4:p.Pro30091Leu

HGVS:

NC_000002.12:g.178546041G>A
NG_011618.3:g.289762C>T
NG_051363.1:g.28215G>A
NM_001256850.1:c.90272C>T
NM_001267550.2:c.95195C>TMANE SELECT
NM_003319.4:c.68000C>T
NM_133378.4:c.87491C>T
NM_133432.3:c.68375C>T
NM_133437.4:c.68576C>T
NP_001243779.1:p.Pro30091Leu
NP_001254479.2:p.Pro31732Leu
NP_003310.4:p.Pro22667Leu
NP_596869.4:p.Pro29164Leu
NP_597676.3:p.Pro22792Leu
NP_597681.4:p.Pro22859Leu
AJ277892.2:g.274436C>T
LRG_391:g.289762C>T
NC_000002.11:g.179410768G>A
NM_001267550.1:c.95195C>T
NM_003319.4:c.68000C>T
NM_133378.4:c.87491C>T

Protein change:

P22667L

Links:

dbSNP: rs753334568

Molecular consequence:

NM_001256850.1:c.90272C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.95195C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.68000C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.87491C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.68375C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.68576C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1G (CMD1G)
Identifiers:: MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:: Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:: MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000543162	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2025)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22526018, 23486992, 23606733, 25500009, 24636144, 25589632, 23975875, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000543162

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2025)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

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

Next generation sequencing for molecular diagnosis of neuromuscular diseases.

Vasli N, Böhm J, Le Gras S, Muller J, Pizot C, Jost B, Echaniz-Laguna A, Laugel V, Tranchant C, Bernard R, Plewniak F, Vicaire S, Levy N, Chelly J, Mandel JL, Biancalana V, Laporte J.

Acta Neuropathol. 2012 Aug;124(2):273-83. doi: 10.1007/s00401-012-0982-8. Epub 2012 Apr 18.

PubMed [citation]

PMID:: 22526018
PMCID:: PMC3400754

Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.

Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer JB, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HC, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery PF, et al.

J Neurol Neurosurg Psychiatry. 2014 Mar;85(3):331-8. doi: 10.1136/jnnp-2012-304728. Epub 2013 Mar 13.

PubMed [citation]

PMID:: 23486992
PMCID:: PMC6558248

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000543162.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 31732 of the TTN protein (p.Pro31732Leu). This variant is present in population databases (rs753334568, gnomAD 0.003%). This missense change has been observed in individual(s) with hereditary myopathy with early respiratory failure (HMERF) (PMID: 22526018, 23486992, 23606733, 25500009). In at least one individual the variant was observed to be de novo. This variant is also known as c.90272C>T (p.Pro30091Leu) and c.68576C>T (p.Pro22859Leu). ClinVar contains an entry for this variant (Variation ID: 132137). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change affects TTN function (PMID: 24636144). This variant is located in the A band of TTN (PMID: 25589632). Variants in this region may be relevant for cardiac or neuromuscular disorders (PMID: 25589632, 23975875). For these reasons, this variant has been classified as Pathogenic.

#	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: Jul 6, 2026

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