Is TTN p.Pro22797= (c.68391G>A) pathogenic?

TTN p.Pro22797= (c.68391G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-11-10). Very rare (popmax 0.005%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro22797= (c.68391G>A)?

TTN p.Pro22797= (c.68391G>A) is associated with Cardiovascular phenotype, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Pro22797= (c.68391G>A) in the general population?

TTN p.Pro22797= (c.68391G>A) is very rare (popmax 0.005%, amr) (gnomAD).

TTN p.Pro22797=

c.68391G>A · rs368985748 · VCV332797

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Cardiovascular phenotype

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 0.24	GERP -5.9, phastCons 0.43
Overall
CADD	0.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,960 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00422% 68/1,613,072 alleles · very rare exomes 62/1,461,008 · genomes 6/152,064 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,987
European (non-Finnish)	0.00475%	21,061
East Asian	0.00447%	22,395
African / African-American	0.00401%	24,958
South Asian	0.00329%	30,353
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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.Pro22797=
Coding: c.68391G>A
MANE Select: NM_001267550
dbSNP: rs368985748
Type: single nucleotide variant
Location: chr2:178578124 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 22797: the ig-like 117 domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J early-onset myopathy with fatal cardiomyopathy

Similar variants

TTN p.Pro22797Leu 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-pro22797 (accessed [today's date]).

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