TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31837	95734;95735;95736	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
N2AB	30196	90811;90812;90813	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
N2A	29269	88030;88031;88032	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
N2B	22772	68539;68540;68541	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
Novex-1	22897	68914;68915;68916	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
Novex-2	22964	69115;69116;69117	chr2:178545601;178545600;178545599	chr2:179410328;179410327;179410326
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-120
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3197
• 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/S	None	None	None	N	0.266	0.145	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.1885	likely_benign	0.2013	benign	-0.479	Destabilizing	0.016	N	0.599	neutral	None	None	None	None	I
N/C	0.1263	likely_benign	0.1377	benign	0.383	Stabilizing	0.824	D	0.687	prob.neutral	None	None	None	None	I
N/D	0.2444	likely_benign	0.2381	benign	-0.497	Destabilizing	0.027	N	0.565	neutral	N	0.477613614	None	None	I
N/E	0.5491	ambiguous	0.5681	pathogenic	-0.52	Destabilizing	0.035	N	0.548	neutral	None	None	None	None	I
N/F	0.5674	likely_pathogenic	0.6026	pathogenic	-0.8	Destabilizing	0.555	D	0.689	prob.neutral	None	None	None	None	I
N/G	0.3282	likely_benign	0.3374	benign	-0.677	Destabilizing	0.035	N	0.457	neutral	None	None	None	None	I
N/H	0.1292	likely_benign	0.1419	benign	-0.776	Destabilizing	0.484	N	0.634	neutral	N	0.484753017	None	None	I
N/I	0.3275	likely_benign	0.3755	ambiguous	-0.031	Destabilizing	0.317	N	0.698	prob.neutral	N	0.462241517	None	None	I
N/K	0.516	ambiguous	0.5514	ambiguous	0.004	Stabilizing	0.027	N	0.546	neutral	N	0.443309039	None	None	I
N/L	0.3088	likely_benign	0.3292	benign	-0.031	Destabilizing	0.149	N	0.687	prob.neutral	None	None	None	None	I
N/M	0.3045	likely_benign	0.34	benign	0.621	Stabilizing	0.791	D	0.683	prob.neutral	None	None	None	None	I
N/P	0.9579	likely_pathogenic	0.9608	pathogenic	-0.154	Destabilizing	0.38	N	0.691	prob.neutral	None	None	None	None	I
N/Q	0.4087	ambiguous	0.4276	ambiguous	-0.614	Destabilizing	0.149	N	0.666	neutral	None	None	None	None	I
N/R	0.5016	ambiguous	0.5362	ambiguous	0.14	Stabilizing	0.149	N	0.675	prob.neutral	None	None	None	None	I
N/S	0.0523	likely_benign	0.0569	benign	-0.26	Destabilizing	None	N	0.266	neutral	N	0.294158807	None	None	I
N/T	0.1326	likely_benign	0.1532	benign	-0.142	Destabilizing	0.027	N	0.531	neutral	N	0.439172656	None	None	I
N/V	0.275	likely_benign	0.3076	benign	-0.154	Destabilizing	0.149	N	0.707	prob.neutral	None	None	None	None	I
N/W	0.8196	likely_pathogenic	0.831	pathogenic	-0.715	Destabilizing	0.935	D	0.733	prob.delet.	None	None	None	None	I
N/Y	0.2217	likely_benign	0.2348	benign	-0.459	Destabilizing	0.484	N	0.679	prob.neutral	N	0.503338778	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.