TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6061	18406;18407;18408	chr2:178730219;178730218;178730217	chr2:179594946;179594945;179594944
N2AB	5744	17455;17456;17457	chr2:178730219;178730218;178730217	chr2:179594946;179594945;179594944
N2A	4817	14674;14675;14676	chr2:178730219;178730218;178730217	chr2:179594946;179594945;179594944
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-44
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.7911
• 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
W/L	rs763108996	-0.411	0.139	N	0.295	0.247	0.547638893815	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	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
W/A	0.3966	ambiguous	0.4394	ambiguous	-1.252	Destabilizing	0.176	N	0.304	neutral	None	None	None	None	N
W/C	0.6596	likely_pathogenic	0.665	pathogenic	-0.066	Destabilizing	0.975	D	0.345	neutral	N	0.473683167	None	None	N
W/D	0.6657	likely_pathogenic	0.7533	pathogenic	1.084	Stabilizing	0.704	D	0.467	neutral	None	None	None	None	N
W/E	0.581	likely_pathogenic	0.6523	pathogenic	1.132	Stabilizing	0.329	N	0.385	neutral	None	None	None	None	N
W/F	0.1957	likely_benign	0.2094	benign	-0.577	Destabilizing	0.543	D	0.328	neutral	None	None	None	None	N
W/G	0.26	likely_benign	0.2924	benign	-1.426	Destabilizing	0.425	N	0.348	neutral	N	0.454577331	None	None	N
W/H	0.5092	ambiguous	0.5362	ambiguous	-0.047	Destabilizing	0.893	D	0.367	neutral	None	None	None	None	N
W/I	0.3556	ambiguous	0.388	ambiguous	-0.73	Destabilizing	0.031	N	0.261	neutral	None	None	None	None	N
W/K	0.5735	likely_pathogenic	0.639	pathogenic	0.019	Stabilizing	0.543	D	0.431	neutral	None	None	None	None	N
W/L	0.2727	likely_benign	0.2846	benign	-0.73	Destabilizing	0.139	N	0.295	neutral	N	0.364456759	None	None	N
W/M	0.4422	ambiguous	0.4579	ambiguous	-0.408	Destabilizing	0.944	D	0.344	neutral	None	None	None	None	N
W/N	0.589	likely_pathogenic	0.6506	pathogenic	-0.187	Destabilizing	0.704	D	0.459	neutral	None	None	None	None	N
W/P	0.9526	likely_pathogenic	0.9661	pathogenic	-0.9	Destabilizing	0.828	D	0.449	neutral	None	None	None	None	N
W/Q	0.4977	ambiguous	0.5247	ambiguous	-0.087	Destabilizing	0.085	N	0.253	neutral	None	None	None	None	N
W/R	0.5142	ambiguous	0.5427	ambiguous	0.27	Stabilizing	0.642	D	0.459	neutral	N	0.407303459	None	None	N
W/S	0.2542	likely_benign	0.2846	benign	-0.783	Destabilizing	0.029	N	0.252	neutral	N	0.339000954	None	None	N
W/T	0.3166	likely_benign	0.3546	ambiguous	-0.69	Destabilizing	0.013	N	0.185	neutral	None	None	None	None	N
W/V	0.3364	likely_benign	0.3507	ambiguous	-0.9	Destabilizing	0.013	N	0.243	neutral	None	None	None	None	N
W/Y	0.3527	ambiguous	0.3707	ambiguous	-0.63	Destabilizing	0.007	N	0.164	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.