STRC Variant c.4976A>C — Misha
TL;DR: Misha carries STRC c.4976A>C, classified VUS-high (REVEL 0.789, near likely-pathogenic). Fudan EENT agrees; long-read sequencing could reclassify to LP and unlock therapeutic eligibility.
Misha carries the STRC variant c.4976A>C (missense, exon 3). This variant affects the stereocilin protein involved in outer hair cell function and hearing.
Classification
- Current classification: VUS-high (Holt lab subclass)
- ACMG criteria: PM3(M) + PP3_Moderate(M) + PM2(S) = 2M + 1S = VUS
- REVEL score: 0.789 (computational prediction supports pathogenicity)
- Note: PP1 was initially incorrectly applied (conservation ≠ co-segregation). Classification corrected from LP to VUS-high.
- Chen Liheng (Fudan EENT) agrees the variant is very close to likely-pathogenic level (April 2026)
Clinical Significance
The variant is in a grey zone — formally VUS but approaching LP. Long-read sequencing at Fudan EENT could help resolve STRC vs pseudo-STRC ambiguity and potentially reclassify.
Connections
- STRC Gene Therapy — [see-also] potential therapeutic avenue
- Shu Yilai Lab — Fudan EENT — [source] research group confirming near-pathogenic status
- 2026-04-07-chen-liheng-strc-reply — [source] email confirming assessment