Is TTN p.Ser6281= (c.18843A>G) pathogenic?

TTN p.Ser6281= (c.18843A>G) is classified Likely benign in TTN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-02). Very rare (popmax 0.00323%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Ser6281= (c.18843A>G) in the general population?

TTN p.Ser6281= (c.18843A>G) is very rare (popmax 0.00323%, nfe) (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.Ser6281=

Q: What condition is associated with TTN p.Ser6281= (c.18843A>G)?

TTN p.Ser6281= (c.18843A>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.18843A>G · rs755958191 · VCV698334

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00323%, nfe)

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 -1.5	GERP -5.8
Overall
CADD	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00323% European (non-Finnish) · 38/1,178,284 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00335% 54/1,611,482 alleles · very rare exomes 43/1,459,334 · genomes 11/152,148 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.025%	3,997
European (non-Finnish)grpmax	0.00323%	31,007

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser6281=
Coding: c.18843A>G
MANE Select: NM_001267550
dbSNP: rs755958191
Type: single nucleotide variant
Location: chr2:178729313 (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-ser6281 (accessed [today's date]).

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