TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31399	94420;94421;94422	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
N2AB	29758	89497;89498;89499	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
N2A	28831	86716;86717;86718	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
N2B	22334	67225;67226;67227	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
Novex-1	22459	67600;67601;67602	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
Novex-2	22526	67801;67802;67803	chr2:178547431;178547430;178547429	chr2:179412158;179412157;179412156
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: Fn3-116
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.529
• 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/L	rs2154146664	None	0.666	N	0.716	0.473	0.607483585054	gnomAD-4.0.0	1.6198E-06	None	None	None	None	N	None	0	0	None	0	2.80978E-05	None	0	0	0	0	0
P/S	None	None	0.134	N	0.311	0.167	0.162503812791	gnomAD-4.0.0	8.40268E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18797E-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	0.055	likely_benign	0.0569	benign	-0.437	Destabilizing	0.022	N	0.272	neutral	N	0.468162326	None	None	N
P/C	0.2697	likely_benign	0.3285	benign	-0.744	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
P/D	0.3875	ambiguous	0.4662	ambiguous	-0.142	Destabilizing	0.949	D	0.599	neutral	None	None	None	None	N
P/E	0.267	likely_benign	0.3391	benign	-0.251	Destabilizing	0.841	D	0.571	neutral	None	None	None	None	N
P/F	0.3741	ambiguous	0.4752	ambiguous	-0.634	Destabilizing	0.974	D	0.808	deleterious	None	None	None	None	N
P/G	0.2107	likely_benign	0.2413	benign	-0.56	Destabilizing	0.725	D	0.631	neutral	None	None	None	None	N
P/H	0.1645	likely_benign	0.195	benign	-0.073	Destabilizing	0.998	D	0.733	deleterious	None	None	None	None	N
P/I	0.2122	likely_benign	0.2621	benign	-0.264	Destabilizing	0.949	D	0.767	deleterious	None	None	None	None	N
P/K	0.2401	likely_benign	0.2985	benign	-0.378	Destabilizing	0.841	D	0.577	neutral	None	None	None	None	N
P/L	0.1094	likely_benign	0.1213	benign	-0.264	Destabilizing	0.666	D	0.716	prob.delet.	N	0.497369397	None	None	N
P/M	0.2363	likely_benign	0.269	benign	-0.391	Destabilizing	0.998	D	0.734	deleterious	None	None	None	None	N
P/N	0.2133	likely_benign	0.2551	benign	-0.192	Destabilizing	0.949	D	0.661	prob.neutral	None	None	None	None	N
P/Q	0.1348	likely_benign	0.1628	benign	-0.417	Destabilizing	0.966	D	0.655	prob.neutral	N	0.480697174	None	None	N
P/R	0.1682	likely_benign	0.2015	benign	0.121	Stabilizing	0.966	D	0.709	prob.delet.	N	0.494948581	None	None	N
P/S	0.084	likely_benign	0.0957	benign	-0.58	Destabilizing	0.134	N	0.311	neutral	N	0.512936909	None	None	N
P/T	0.0756	likely_benign	0.0816	benign	-0.584	Destabilizing	0.051	N	0.31	neutral	N	0.487982536	None	None	N
P/V	0.1331	likely_benign	0.1502	benign	-0.287	Destabilizing	0.725	D	0.635	neutral	None	None	None	None	N
P/W	0.585	likely_pathogenic	0.6789	pathogenic	-0.694	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
P/Y	0.371	ambiguous	0.4699	ambiguous	-0.397	Destabilizing	0.991	D	0.807	deleterious	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.