TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5362	16309;16310;16311	chr2:178733092;178733091;178733090	chr2:179597819;179597818;179597817
N2AB	5045	15358;15359;15360	chr2:178733092;178733091;178733090	chr2:179597819;179597818;179597817
N2A	4118	12577;12578;12579	chr2:178733092;178733091;178733090	chr2:179597819;179597818;179597817
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: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-37
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4279
• 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	rs2080839872	None	0.454	N	0.449	0.236	0.633181949713	gnomAD-4.0.0	1.62566E-06	None	None	None	None	N	None	0	2.34544E-05	None	0	0	None	0	0	0	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	0.0844	likely_benign	0.0783	benign	-0.904	Destabilizing	0.005	N	0.218	neutral	N	0.489748697	None	None	N
P/C	0.573	likely_pathogenic	0.5322	ambiguous	-0.647	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
P/D	0.5163	ambiguous	0.448	ambiguous	-0.066	Destabilizing	0.842	D	0.402	neutral	None	None	None	None	N
P/E	0.3168	likely_benign	0.2709	benign	-0.098	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	N
P/F	0.5214	ambiguous	0.4718	ambiguous	-0.668	Destabilizing	0.949	D	0.523	neutral	None	None	None	None	N
P/G	0.2842	likely_benign	0.2688	benign	-1.167	Destabilizing	0.525	D	0.421	neutral	None	None	None	None	N
P/H	0.2224	likely_benign	0.1995	benign	-0.63	Destabilizing	0.997	D	0.483	neutral	N	0.486383105	None	None	N
P/I	0.3086	likely_benign	0.2725	benign	-0.315	Destabilizing	0.904	D	0.482	neutral	None	None	None	None	N
P/K	0.3146	likely_benign	0.2782	benign	-0.6	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	N
P/L	0.144	likely_benign	0.1326	benign	-0.315	Destabilizing	0.454	N	0.449	neutral	N	0.503024639	None	None	N
P/M	0.288	likely_benign	0.2658	benign	-0.33	Destabilizing	0.325	N	0.384	neutral	None	None	None	None	N
P/N	0.308	likely_benign	0.2803	benign	-0.338	Destabilizing	0.949	D	0.475	neutral	None	None	None	None	N
P/Q	0.1508	likely_benign	0.1369	benign	-0.483	Destabilizing	0.974	D	0.449	neutral	None	None	None	None	N
P/R	0.2292	likely_benign	0.2039	benign	-0.182	Destabilizing	0.966	D	0.479	neutral	N	0.472048371	None	None	N
P/S	0.1263	likely_benign	0.1155	benign	-0.915	Destabilizing	0.062	N	0.216	neutral	N	0.495578591	None	None	N
P/T	0.1063	likely_benign	0.0954	benign	-0.83	Destabilizing	0.669	D	0.363	neutral	N	0.48884462	None	None	N
P/V	0.2047	likely_benign	0.1816	benign	-0.474	Destabilizing	0.728	D	0.424	neutral	None	None	None	None	N
P/W	0.7092	likely_pathogenic	0.6605	pathogenic	-0.789	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
P/Y	0.4474	ambiguous	0.3933	ambiguous	-0.488	Destabilizing	0.991	D	0.514	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.