Is TTN p.Pro12960= (c.38880A>G) pathogenic?

TTN p.Pro12960= (c.38880A>G) is classified Benign in TTN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

What condition is associated with TTN p.Pro12960= (c.38880A>G)?

TTN p.Pro12960= (c.38880A>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

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.Pro12960=

Q: How common is TTN p.Pro12960= (c.38880A>G) in the general population?

TTN p.Pro12960= (c.38880A>G) is common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.38880A>G · rs2742354 · VCV413166

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3.7
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.16% East Asian · 4,102/44,758 alleles

Filtering AF 8.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.84%

Overall 2.57% 41,251/1,606,042 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	9.16%	11
Finnishnot grpmax-eligible	4.84%	21
Amishnot grpmax-eligible	3.07%	33
Admixed American	3.03%	33
South Asian	2.83%	35
Remaining individualsnot grpmax-eligible	2.63%	38
European (non-Finnish)	2.31%	43
Ashkenazi Jewishnot grpmax-eligible	1.58%	63
Middle Eastern	1.42%	70
African / African-American	0.48%	208

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.Pro12960=
Coding: c.38880A>G
MANE Select: NM_001267550
dbSNP: rs2742354
Type: single nucleotide variant
Location: chr2:178652927 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 12960: the ig-like 86 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.Pro12960Leu 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-pro12960 (accessed [today's date]).

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