TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29872	89839;89840;89841	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
N2AB	28231	84916;84917;84918	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
N2A	27304	82135;82136;82137	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
N2B	20807	62644;62645;62646	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
Novex-1	20932	63019;63020;63021	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
Novex-2	20999	63220;63221;63222	chr2:178553286;178553285;178553284	chr2:179418013;179418012;179418011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-147
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.3271
• 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
T/K	None	None	0.497	N	0.611	0.231	0.280987212366	gnomAD-4.0.0	6.8614E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99467E-07	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
T/A	0.1257	likely_benign	0.1249	benign	-0.936	Destabilizing	0.055	N	0.552	neutral	N	0.50720408	None	None	N
T/C	0.4255	ambiguous	0.4445	ambiguous	-0.644	Destabilizing	0.968	D	0.619	neutral	None	None	None	None	N
T/D	0.6102	likely_pathogenic	0.5898	pathogenic	-0.334	Destabilizing	0.726	D	0.634	neutral	None	None	None	None	N
T/E	0.4361	ambiguous	0.4308	ambiguous	-0.292	Destabilizing	0.726	D	0.615	neutral	None	None	None	None	N
T/F	0.2368	likely_benign	0.2477	benign	-0.865	Destabilizing	0.567	D	0.691	prob.neutral	None	None	None	None	N
T/G	0.4138	ambiguous	0.4013	ambiguous	-1.238	Destabilizing	0.567	D	0.67	neutral	None	None	None	None	N
T/H	0.2649	likely_benign	0.2848	benign	-1.433	Destabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	N
T/I	0.1365	likely_benign	0.1418	benign	-0.211	Destabilizing	0.001	N	0.403	neutral	N	0.500344452	None	None	N
T/K	0.2655	likely_benign	0.2779	benign	-0.757	Destabilizing	0.497	N	0.611	neutral	N	0.506526304	None	None	N
T/L	0.1094	likely_benign	0.1127	benign	-0.211	Destabilizing	0.026	N	0.513	neutral	None	None	None	None	N
T/M	0.1043	likely_benign	0.1048	benign	-0.035	Destabilizing	0.026	N	0.491	neutral	None	None	None	None	N
T/N	0.1741	likely_benign	0.1711	benign	-0.835	Destabilizing	0.726	D	0.555	neutral	None	None	None	None	N
T/P	0.8277	likely_pathogenic	0.7621	pathogenic	-0.42	Destabilizing	0.859	D	0.64	neutral	D	0.552428718	None	None	N
T/Q	0.2519	likely_benign	0.2661	benign	-0.921	Destabilizing	0.567	D	0.641	neutral	None	None	None	None	N
T/R	0.2246	likely_benign	0.2382	benign	-0.582	Destabilizing	0.497	N	0.637	neutral	D	0.524901421	None	None	N
T/S	0.1299	likely_benign	0.1326	benign	-1.136	Destabilizing	0.22	N	0.549	neutral	N	0.483916016	None	None	N
T/V	0.1279	likely_benign	0.1356	benign	-0.42	Destabilizing	0.001	N	0.254	neutral	None	None	None	None	N
T/W	0.6314	likely_pathogenic	0.6317	pathogenic	-0.801	Destabilizing	0.968	D	0.728	prob.delet.	None	None	None	None	N
T/Y	0.2942	likely_benign	0.3179	benign	-0.559	Destabilizing	0.726	D	0.699	prob.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.