TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5288	16087;16088;16089	chr2:178733431;178733430;178733429	chr2:179598158;179598157;179598156
N2AB	4971	15136;15137;15138	chr2:178733431;178733430;178733429	chr2:179598158;179598157;179598156
N2A	4044	12355;12356;12357	chr2:178733431;178733430;178733429	chr2:179598158;179598157;179598156
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-36
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.7738
• 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
P/L	None	None	1.0	D	0.639	0.728	0.895153570487	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79895E-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
P/A	0.4158	ambiguous	0.5503	ambiguous	-0.355	Destabilizing	1.0	D	0.669	neutral	D	0.674896769	None	None	I
P/C	0.9428	likely_pathogenic	0.9691	pathogenic	-0.631	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
P/D	0.9135	likely_pathogenic	0.9595	pathogenic	-0.368	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
P/E	0.7967	likely_pathogenic	0.9041	pathogenic	-0.493	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
P/F	0.9644	likely_pathogenic	0.9859	pathogenic	-0.696	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
P/G	0.8096	likely_pathogenic	0.871	pathogenic	-0.443	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
P/H	0.8503	likely_pathogenic	0.9258	pathogenic	-0.016	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
P/I	0.8552	likely_pathogenic	0.9326	pathogenic	-0.273	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
P/K	0.8792	likely_pathogenic	0.9532	pathogenic	-0.372	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
P/L	0.5818	likely_pathogenic	0.786	pathogenic	-0.273	Destabilizing	1.0	D	0.639	neutral	D	0.812980435	None	None	I
P/M	0.8129	likely_pathogenic	0.9122	pathogenic	-0.433	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	I
P/N	0.9089	likely_pathogenic	0.9504	pathogenic	-0.102	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
P/Q	0.7417	likely_pathogenic	0.874	pathogenic	-0.36	Destabilizing	1.0	D	0.647	neutral	D	0.749533781	None	None	I
P/R	0.77	likely_pathogenic	0.9018	pathogenic	0.142	Stabilizing	1.0	D	0.633	neutral	D	0.761664472	None	None	I
P/S	0.6639	likely_pathogenic	0.7735	pathogenic	-0.412	Destabilizing	1.0	D	0.652	neutral	D	0.730104398	None	None	I
P/T	0.5147	ambiguous	0.6299	pathogenic	-0.443	Destabilizing	1.0	D	0.647	neutral	D	0.712968835	None	None	I
P/V	0.7162	likely_pathogenic	0.8384	pathogenic	-0.269	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
P/W	0.9733	likely_pathogenic	0.9905	pathogenic	-0.758	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
P/Y	0.9552	likely_pathogenic	0.981	pathogenic	-0.463	Destabilizing	1.0	D	0.659	neutral	None	None	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.