Is TTN p.Pro16286= (c.48858T>C) pathogenic?

TTN p.Pro16286= (c.48858T>C) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). Very rare (popmax 0.00224%, eas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro16286= (c.48858T>C) in the general population?

TTN p.Pro16286= (c.48858T>C) is very rare (popmax 0.00224%, 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.Pro16286=

Q: What condition is associated with TTN p.Pro16286= (c.48858T>C)?

TTN p.Pro16286= (c.48858T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.48858T>C · rs771942101 · VCV3761773

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.4	GERP -5.5
Overall
CADD	0.545	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,580 alleles

Overall 0.000124% 2/1,612,262 alleles · very rare exomes 1/1,460,382 · genomes 1/151,880 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,580
Admixed American	0.00167%	59,856

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.Pro16286=
Coding: c.48858T>C
MANE Select: NM_001267550
dbSNP: rs771942101
Type: single nucleotide variant
Location: chr2:178614656 (GRCh38)

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

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-pro16286 (accessed [today's date]).

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