Is TTN p.Pro13271= (c.39813A>G) pathogenic?

TTN p.Pro13271= (c.39813A>G) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0413%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

What condition is associated with TTN p.Pro13271= (c.39813A>G)?

TTN p.Pro13271= (c.39813A>G) 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.Pro13271= (c.39813A>G) in the general population?

TTN p.Pro13271= (c.39813A>G) is ultra-rare (popmax 0.0413%, 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.Pro13271=

c.39813A>G · rs373429851 · VCV284678

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, 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.
REVEL	0.017	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -1.7
Overall
CADD	1.961	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0413% European (non-Finnish) · 479/1,160,398 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.037%

Overall 0.032% 505/1,578,470 alleles · ultra-rare exomes 485/1,426,206 · genomes 20/152,264 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0413%	2,423
Remaining individualsnot grpmax-eligible	0.036%	2,775
African / African-American	0.0027%	37,063
Admixed American	0.0018%	55,620
Finnishnot grpmax-eligible	0.00161%	62,042

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.Pro13271=
Coding: c.39813A>G
MANE Select: NM_001267550
dbSNP: rs373429851
Type: single nucleotide variant
Location: chr2:178650168 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 13271: the ig-like 88 domain

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

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Pro13271Leu 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-pro13271 (accessed [today's date]).

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