Is TTN p.Pro12818= (c.38454C>T) pathogenic?

TTN p.Pro12818= (c.38454C>T) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-23). Very rare (popmax 0.00457%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro12818= (c.38454C>T) in the general population?

TTN p.Pro12818= (c.38454C>T) is very rare (popmax 0.00457%, eas) (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.Pro12818=

Q: What condition is associated with TTN p.Pro12818= (c.38454C>T)?

TTN p.Pro12818= (c.38454C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.38454C>T · rs2063594484 · VCV1159439

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00457%, eas)

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	3.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00457% East Asian · 2/43,752 alleles

Filtering AF 0.000758% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000283%

Overall 0.000698% 11/1,575,418 alleles · very rare exomes 11/1,428,526 · genomes 0/146,892 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00457%	21,876
South Asian	0.00224%	44,637
Remaining individualsnot grpmax-eligible	0.00163%	61,444
African / African-American	0.00138%	72,426
European (non-Finnish)	0.000428%	233,802

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.Pro12818=
Coding: c.38454C>T
MANE Select: NM_001267550
dbSNP: rs2063594484
Type: single nucleotide variant
Location: chr2:178654022 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 12818: the ig-like 85 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: dilated cardiomyopathy 1G

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

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
TTN c.107377+1G>C 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-pro12818 (accessed [today's date]).

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