TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24728	74407;74408;74409	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
N2AB	23087	69484;69485;69486	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
N2A	22160	66703;66704;66705	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
N2B	15663	47212;47213;47214	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
Novex-1	15788	47587;47588;47589	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
Novex-2	15855	47788;47789;47790	chr2:178571950;178571949;178571948	chr2:179436677;179436676;179436675
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-133
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.9876
• Predicted PPI site: I

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/P	rs1708337255	None	0.97	N	0.633	0.506	0.80197800866	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	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
L/A	0.2393	likely_benign	0.2769	benign	-0.942	Destabilizing	0.754	D	0.563	neutral	None	None	None	None	I
L/C	0.556	ambiguous	0.6157	pathogenic	-0.705	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	I
L/D	0.7828	likely_pathogenic	0.8323	pathogenic	-0.207	Destabilizing	0.956	D	0.631	neutral	None	None	None	None	I
L/E	0.4045	ambiguous	0.466	ambiguous	-0.261	Destabilizing	0.915	D	0.624	neutral	None	None	None	None	I
L/F	0.1849	likely_benign	0.2296	benign	-0.702	Destabilizing	0.956	D	0.479	neutral	None	None	None	None	I
L/G	0.601	likely_pathogenic	0.6533	pathogenic	-1.17	Destabilizing	0.956	D	0.624	neutral	None	None	None	None	I
L/H	0.2282	likely_benign	0.2846	benign	-0.323	Destabilizing	0.994	D	0.657	neutral	None	None	None	None	I
L/I	0.1317	likely_benign	0.1391	benign	-0.438	Destabilizing	0.16	N	0.286	neutral	None	None	None	None	I
L/K	0.1715	likely_benign	0.2036	benign	-0.531	Destabilizing	0.043	N	0.483	neutral	None	None	None	None	I
L/M	0.1054	likely_benign	0.1105	benign	-0.458	Destabilizing	0.489	N	0.455	neutral	D	0.523130552	None	None	I
L/N	0.4481	ambiguous	0.4956	ambiguous	-0.358	Destabilizing	0.956	D	0.631	neutral	None	None	None	None	I
L/P	0.233	likely_benign	0.2608	benign	-0.572	Destabilizing	0.97	D	0.633	neutral	N	0.485959031	None	None	I
L/Q	0.1219	likely_benign	0.1393	benign	-0.552	Destabilizing	0.942	D	0.611	neutral	N	0.435836854	None	None	I
L/R	0.1569	likely_benign	0.1921	benign	0.041	Stabilizing	0.89	D	0.61	neutral	N	0.409690403	None	None	I
L/S	0.3449	ambiguous	0.4037	ambiguous	-0.905	Destabilizing	0.956	D	0.545	neutral	None	None	None	None	I
L/T	0.2383	likely_benign	0.2822	benign	-0.843	Destabilizing	0.956	D	0.485	neutral	None	None	None	None	I
L/V	0.115	likely_benign	0.1255	benign	-0.572	Destabilizing	0.489	N	0.547	neutral	N	0.438205156	None	None	I
L/W	0.3271	likely_benign	0.3934	ambiguous	-0.715	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	I
L/Y	0.4046	ambiguous	0.4665	ambiguous	-0.481	Destabilizing	0.993	D	0.503	neutral	None	None	None	None	I

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.