Is TTN p.Pro11615= (c.34845C>T) pathogenic?

TTN p.Pro11615= (c.34845C>T) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0638%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro11615= (c.34845C>T) in the general population?

TTN p.Pro11615= (c.34845C>T) is ultra-rare (popmax 0.0638%, 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.Pro11615=

Q: What condition is associated with TTN p.Pro11615= (c.34845C>T)?

TTN p.Pro11615= (c.34845C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, cardiomyopathy, dilated cardiomyopathy 1G (ClinVar).

c.34845C>T · rs368781863 · VCV166100

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0638%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.72	GERP -5.1
Overall
CADD	0.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0638% European (non-Finnish) · 752/1,178,206 alleles

Filtering AF 0.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.0506% 815/1,611,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0638%	1,567
South Asian	0.0341%	2,932
Remaining individualsnot grpmax-eligible	0.0241%	4,158
Admixed American	0.0201%	4,971
African / African-American	0.00667%	14,983

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.Pro11615=
Coding: c.34845C>T
MANE Select: NM_001267550
dbSNP: rs368781863
Type: single nucleotide variant
Location: chr2:178672645 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 11615: 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: cardiomyopathy dilated cardiomyopathy 1G

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Pro11615Ser Uncertain significance ★ same residue
TTN c.100171+1G>A Likely pathogenic ★★ same condition
TTN c.100766-1G>T Likely pathogenic ★★ same condition
TTN c.100766-2A>T Likely pathogenic ★★ same condition
TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same condition
TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.107224-1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.107377+1G>A Pathogenic/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-pro11615 (accessed [today's date]).

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