TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35754	107485;107486;107487	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
N2AB	34113	102562;102563;102564	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
N2A	33186	99781;99782;99783	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
N2B	26689	80290;80291;80292	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
Novex-1	26814	80665;80666;80667	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
Novex-2	26881	80866;80867;80868	chr2:178528391;178528390;178528389	chr2:179393118;179393117;179393116
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-168
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.9315
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/K	rs1687469924	None	None	N	0.161	0.089	0.0551355673512	gnomAD-4.0.0	3.18203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71546E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.3842	ambiguous	0.3425	ambiguous	-0.042	Destabilizing	0.016	N	0.386	neutral	None	None	None	None	N
R/C	0.39	ambiguous	0.4351	ambiguous	-0.303	Destabilizing	0.864	D	0.288	neutral	None	None	None	None	N
R/D	0.6274	likely_pathogenic	0.5759	pathogenic	-0.318	Destabilizing	0.072	N	0.457	neutral	None	None	None	None	N
R/E	0.3469	ambiguous	0.2964	benign	-0.284	Destabilizing	0.016	N	0.381	neutral	None	None	None	None	N
R/F	0.7361	likely_pathogenic	0.7053	pathogenic	-0.376	Destabilizing	0.214	N	0.331	neutral	None	None	None	None	N
R/G	0.1783	likely_benign	0.1558	benign	-0.17	Destabilizing	0.055	N	0.433	neutral	N	0.364466175	None	None	N
R/H	0.1659	likely_benign	0.1778	benign	-0.616	Destabilizing	0.356	N	0.38	neutral	None	None	None	None	N
R/I	0.4058	ambiguous	0.359	ambiguous	0.251	Stabilizing	0.029	N	0.416	neutral	N	0.448031708	None	None	N
R/K	0.0944	likely_benign	0.0878	benign	-0.238	Destabilizing	None	N	0.161	neutral	N	0.389175405	None	None	N
R/L	0.3777	ambiguous	0.355	ambiguous	0.251	Stabilizing	None	N	0.29	neutral	None	None	None	None	N
R/M	0.3546	ambiguous	0.3158	benign	-0.114	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	N
R/N	0.5361	ambiguous	0.4966	ambiguous	-0.127	Destabilizing	0.072	N	0.381	neutral	None	None	None	None	N
R/P	0.5401	ambiguous	0.5293	ambiguous	0.171	Stabilizing	0.356	N	0.401	neutral	None	None	None	None	N
R/Q	0.1102	likely_benign	0.1075	benign	-0.184	Destabilizing	0.003	N	0.26	neutral	None	None	None	None	N
R/S	0.4205	ambiguous	0.3714	ambiguous	-0.332	Destabilizing	0.029	N	0.407	neutral	N	0.400525762	None	None	N
R/T	0.2731	likely_benign	0.2404	benign	-0.198	Destabilizing	0.055	N	0.449	neutral	N	0.402355346	None	None	N
R/V	0.5021	ambiguous	0.456	ambiguous	0.171	Stabilizing	0.038	N	0.432	neutral	None	None	None	None	N
R/W	0.2762	likely_benign	0.276	benign	-0.545	Destabilizing	0.864	D	0.287	neutral	None	None	None	None	N
R/Y	0.5756	likely_pathogenic	0.5659	pathogenic	-0.148	Destabilizing	0.628	D	0.354	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.