Is TTN p.Pro11501fs (c.34499dup) pathogenic?

TTN p.Pro11501fs (c.34499dup) is classified Uncertain significance in TTN (ClinVar, Single submitter, 3 submitters; last evaluated 2022-01-05). Very rare (popmax 9.08e-05%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

What condition is associated with TTN p.Pro11501fs (c.34499dup)?

TTN p.Pro11501fs (c.34499dup) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

How common is TTN p.Pro11501fs (c.34499dup) in the general population?

TTN p.Pro11501fs (c.34499dup) is very rare (popmax 9.08e-05%, nfe) (gnomAD).

How is Titin-related limb-girdle muscular dystrophy R10 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TTN p.Pro11501fs

c.34499dup · rs1560284392 · VCV1284808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.08e-05%, nfe)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 149 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP -1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.08e-05% European (non-Finnish) · 1/1,100,740 alleles

Overall 0.000157% 2/1,276,856 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00181%	55,320
European (non-Finnish)grpmax	9.08e-05%	1,100,740

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TTN
Protein: p.Pro11501fs
Coding: c.34499dup
MANE Select: NM_001267550
dbSNP: rs1560284392
Type: Duplication
Location: chr2:178675708 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 11501: the 'disordered' region

Full TTN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G early-onset myopathy with fatal cardiomyopathy hypertrophic cardiomyopathy 9

For Titin-related limb-girdle muscular dystrophy R10 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Ala30898Ter Likely pathogenic ★★ same condition
TTN p.Arg1003fs Likely pathogenic ★★ same condition
TTN p.Arg17000Ter Pathogenic/Likely pathogenic ★★ same condition
TTN p.Arg26192fs Likely pathogenic ★★ same condition
TTN p.Arg27776fs Likely pathogenic ★★ same condition
TTN p.Asn16133Ter Pathogenic/Likely pathogenic ★★ same condition
TTN p.Asn18739delinsIleTer Likely pathogenic ★★ same condition
TTN p.Asn20321fs Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ttn-p-pro11501fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown