TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15228	45907;45908;45909	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
N2AB	13587	40984;40985;40986	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
N2A	12660	38203;38204;38205	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
N2B	6163	18712;18713;18714	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
Novex-1	6288	19087;19088;19089	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
Novex-2	6355	19288;19289;19290	chr2:178620928;178620927;178620926	chr2:179485655;179485654;179485653
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-104
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.5402
• Predicted PPI site: I

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
N/I	None	None	0.971	N	0.702	0.516	0.772084405115	gnomAD-4.0.0	1.59407E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86257E-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
N/A	0.3516	ambiguous	0.3729	ambiguous	-0.838	Destabilizing	0.754	D	0.573	neutral	None	None	None	None	I
N/C	0.4118	ambiguous	0.3934	ambiguous	0.057	Stabilizing	0.998	D	0.673	neutral	None	None	None	None	I
N/D	0.2501	likely_benign	0.2765	benign	-0.28	Destabilizing	0.822	D	0.495	neutral	N	0.502732099	None	None	I
N/E	0.5462	ambiguous	0.5708	pathogenic	-0.166	Destabilizing	0.86	D	0.491	neutral	None	None	None	None	I
N/F	0.6507	likely_pathogenic	0.6285	pathogenic	-0.53	Destabilizing	0.956	D	0.705	prob.neutral	None	None	None	None	I
N/G	0.5004	ambiguous	0.5196	ambiguous	-1.197	Destabilizing	0.754	D	0.502	neutral	None	None	None	None	I
N/H	0.1033	likely_benign	0.0962	benign	-0.873	Destabilizing	0.032	N	0.341	neutral	N	0.514826976	None	None	I
N/I	0.2341	likely_benign	0.2468	benign	0.082	Stabilizing	0.971	D	0.702	prob.neutral	N	0.515612042	None	None	I
N/K	0.4492	ambiguous	0.463	ambiguous	-0.142	Destabilizing	0.698	D	0.51	neutral	N	0.506871151	None	None	I
N/L	0.3004	likely_benign	0.2866	benign	0.082	Stabilizing	0.956	D	0.661	neutral	None	None	None	None	I
N/M	0.4707	ambiguous	0.4901	ambiguous	0.436	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	I
N/P	0.8497	likely_pathogenic	0.841	pathogenic	-0.194	Destabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	I
N/Q	0.42	ambiguous	0.4328	ambiguous	-0.667	Destabilizing	0.956	D	0.561	neutral	None	None	None	None	I
N/R	0.4287	ambiguous	0.4227	ambiguous	-0.242	Destabilizing	0.956	D	0.539	neutral	None	None	None	None	I
N/S	0.0858	likely_benign	0.0937	benign	-0.821	Destabilizing	0.058	N	0.368	neutral	N	0.495394783	None	None	I
N/T	0.1451	likely_benign	0.1499	benign	-0.502	Destabilizing	0.698	D	0.493	neutral	N	0.500244014	None	None	I
N/V	0.2841	likely_benign	0.2941	benign	-0.194	Destabilizing	0.956	D	0.698	prob.neutral	None	None	None	None	I
N/W	0.878	likely_pathogenic	0.8639	pathogenic	-0.284	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
N/Y	0.2329	likely_benign	0.2244	benign	-0.071	Destabilizing	0.89	D	0.689	prob.neutral	N	0.510880949	None	None	I

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.