Is TTN p.Phe4983= (c.14949C>T) pathogenic?

TTN p.Phe4983= (c.14949C>T) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-03). Very rare (popmax 0.00914%, sas); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Phe4983= (c.14949C>T)?

TTN p.Phe4983= (c.14949C>T) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Phe4983= (c.14949C>T) in the general population?

TTN p.Phe4983= (c.14949C>T) is very rare (popmax 0.00914%, sas) (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.Phe4983=

c.14949C>T · rs758324605 · VCV535338

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00914%, sas)

Conditions

dilated cardiomyopathy 1G

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 0.17	GERP -5.7, phastCons 0.076
Overall
CADD	5.534	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00914% South Asian · 8/87,562 alleles

Filtering AF 0.00452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00323%

Overall 0.000947% 15/1,583,640 alleles · very rare exomes 10/1,431,340 · genomes 5/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00914%	10,945
East Asian	0.00455%	21,963
Admixed American	0.00363%	27,526
African / African-American	0.00269%	37,192
European (non-Finnish)	8.6e-05%	1,162,570

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.Phe4983=
Coding: c.14949C>T
MANE Select: NM_001267550
dbSNP: rs758324605
Type: single nucleotide variant
Location: chr2:178734975 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 4983: the ig-like 30 domain

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.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-phe4983 (accessed [today's date]).

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