Is TTN p.Pro200fs (c.599del) pathogenic?

TTN p.Pro200fs (c.599del) is classified Likely pathogenic in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Absent from gnomAD; Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Pro200fs (c.599del)?

TTN p.Pro200fs (c.599del) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro200fs (c.599del) in the general population?

TTN p.Pro200fs (c.599del) is absent from gnomAD (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

TTN p.Pro200fs

c.599del · rs2534325318 · VCV2069012

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dilated cardiomyopathy 1G

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 5 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.055	GERP -3, phastCons 0.32

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TTN
Protein: p.Pro200fs
Coding: c.599del
MANE Select: NM_001267550
dbSNP: rs2534325318
Type: Deletion
Location: chr2:178799895 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 200: a β-strand

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

Disease context

dilated cardiomyopathy 1G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2J

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

TTN c.32888-1del Likely pathogenic ★★ same condition
TTN c.49648+2del Pathogenic ★★ same condition
TTN c.80003_80028+4del Likely pathogenic ★★ same condition
TTN c.86822-1del Likely pathogenic ★★ same condition
TTN p.Ala14213fs Likely pathogenic ★★ same condition
TTN p.Ala18013fs Likely pathogenic ★★ same condition
TTN p.Ala18143fs Likely pathogenic ★★ same condition
TTN p.Ala19403fs 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-pro200fs (accessed [today's date]).

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