TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14282	43069;43070;43071	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
N2AB	12641	38146;38147;38148	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
N2A	11714	35365;35366;35367	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
N2B	5217	15874;15875;15876	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
Novex-1	5342	16249;16250;16251	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
Novex-2	5409	16450;16451;16452	chr2:178633515;178633514;178633513	chr2:179498242;179498241;179498240
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-93
• Domain position: 52
• Structural Position: 134
• Q(SASA): 0.4576
• 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
L/V	None	None	0.891	N	0.309	0.099	0.403040389579	gnomAD-4.0.0	3.1844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86558E-05	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
L/A	0.1935	likely_benign	0.209	benign	-1.385	Destabilizing	0.688	D	0.347	neutral	None	None	None	None	N
L/C	0.4818	ambiguous	0.5039	ambiguous	-0.76	Destabilizing	0.998	D	0.449	neutral	None	None	None	None	N
L/D	0.5592	ambiguous	0.5967	pathogenic	-0.913	Destabilizing	0.949	D	0.497	neutral	None	None	None	None	N
L/E	0.2954	likely_benign	0.3313	benign	-0.979	Destabilizing	0.728	D	0.482	neutral	None	None	None	None	N
L/F	0.1348	likely_benign	0.1386	benign	-1.217	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	N
L/G	0.3562	ambiguous	0.3871	ambiguous	-1.627	Destabilizing	0.842	D	0.483	neutral	None	None	None	None	N
L/H	0.1703	likely_benign	0.1869	benign	-0.837	Destabilizing	0.993	D	0.502	neutral	None	None	None	None	N
L/I	0.1075	likely_benign	0.106	benign	-0.828	Destabilizing	0.915	D	0.357	neutral	None	None	None	None	N
L/K	0.1166	likely_benign	0.1391	benign	-0.776	Destabilizing	0.007	N	0.261	neutral	None	None	None	None	N
L/M	0.122	likely_benign	0.1145	benign	-0.514	Destabilizing	0.989	D	0.447	neutral	N	0.511224395	None	None	N
L/N	0.2022	likely_benign	0.2202	benign	-0.497	Destabilizing	0.949	D	0.495	neutral	None	None	None	None	N
L/P	0.1979	likely_benign	0.2445	benign	-0.982	Destabilizing	0.966	D	0.525	neutral	N	0.466667583	None	None	N
L/Q	0.0985	likely_benign	0.1143	benign	-0.798	Destabilizing	0.934	D	0.484	neutral	N	0.485538001	None	None	N
L/R	0.1177	likely_benign	0.1419	benign	-0.11	Destabilizing	0.012	N	0.351	neutral	N	0.454582937	None	None	N
L/S	0.1679	likely_benign	0.1791	benign	-1.04	Destabilizing	0.842	D	0.445	neutral	None	None	None	None	N
L/T	0.1507	likely_benign	0.1572	benign	-1.001	Destabilizing	0.842	D	0.384	neutral	None	None	None	None	N
L/V	0.1103	likely_benign	0.115	benign	-0.982	Destabilizing	0.891	D	0.309	neutral	N	0.485117775	None	None	N
L/W	0.227	likely_benign	0.2496	benign	-1.201	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	N
L/Y	0.2845	likely_benign	0.2965	benign	-0.977	Destabilizing	0.991	D	0.443	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.