TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18010	54253;54254;54255	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
N2AB	16369	49330;49331;49332	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
N2A	15442	46549;46550;46551	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
N2B	8945	27058;27059;27060	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
Novex-1	9070	27433;27434;27435	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
Novex-2	9137	27634;27635;27636	chr2:178605149;178605148;178605147	chr2:179469876;179469875;179469874
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-114
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.6504
• 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
P/S	None	None	0.022	N	0.281	0.099	0.16115917748	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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	0.0584	likely_benign	0.0666	benign	-0.627	Destabilizing	0.454	N	0.351	neutral	N	0.502364838	None	None	N
P/C	0.4401	ambiguous	0.4887	ambiguous	-0.665	Destabilizing	0.998	D	0.442	neutral	None	None	None	None	N
P/D	0.3801	ambiguous	0.4068	ambiguous	-0.408	Destabilizing	0.842	D	0.34	neutral	None	None	None	None	N
P/E	0.2413	likely_benign	0.265	benign	-0.493	Destabilizing	0.842	D	0.304	neutral	None	None	None	None	N
P/F	0.4795	ambiguous	0.5267	ambiguous	-0.695	Destabilizing	0.974	D	0.45	neutral	None	None	None	None	N
P/G	0.2373	likely_benign	0.2536	benign	-0.806	Destabilizing	0.728	D	0.357	neutral	None	None	None	None	N
P/H	0.2239	likely_benign	0.2343	benign	-0.386	Destabilizing	0.997	D	0.431	neutral	N	0.468720714	None	None	N
P/I	0.2499	likely_benign	0.2879	benign	-0.291	Destabilizing	0.949	D	0.449	neutral	None	None	None	None	N
P/K	0.2248	likely_benign	0.2455	benign	-0.636	Destabilizing	0.842	D	0.313	neutral	None	None	None	None	N
P/L	0.1357	likely_benign	0.1464	benign	-0.291	Destabilizing	0.669	D	0.384	neutral	N	0.455425398	None	None	N
P/M	0.234	likely_benign	0.2622	benign	-0.389	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	N
P/N	0.2408	likely_benign	0.2627	benign	-0.381	Destabilizing	0.842	D	0.395	neutral	None	None	None	None	N
P/Q	0.1498	likely_benign	0.1572	benign	-0.581	Destabilizing	0.974	D	0.373	neutral	None	None	None	None	N
P/R	0.2062	likely_benign	0.2156	benign	-0.141	Destabilizing	0.934	D	0.437	neutral	N	0.454224084	None	None	N
P/S	0.1091	likely_benign	0.1187	benign	-0.759	Destabilizing	0.022	N	0.281	neutral	N	0.464865243	None	None	N
P/T	0.0693	likely_benign	0.0829	benign	-0.737	Destabilizing	0.022	N	0.284	neutral	N	0.484491153	None	None	N
P/V	0.1563	likely_benign	0.177	benign	-0.367	Destabilizing	0.728	D	0.369	neutral	None	None	None	None	N
P/W	0.6793	likely_pathogenic	0.7156	pathogenic	-0.813	Destabilizing	0.998	D	0.524	neutral	None	None	None	None	N
P/Y	0.4304	ambiguous	0.4686	ambiguous	-0.517	Destabilizing	0.991	D	0.451	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.