TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6233	18922;18923;18924	chr2:178729459;178729458;178729457	chr2:179594186;179594185;179594184
N2AB	5916	17971;17972;17973	chr2:178729459;178729458;178729457	chr2:179594186;179594185;179594184
N2A	4989	15190;15191;15192	chr2:178729459;178729458;178729457	chr2:179594186;179594185;179594184
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-46
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.2674
• 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/P	None	None	0.966	N	0.654	0.377	0.76439084235	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.4207	ambiguous	0.475	ambiguous	-2.392	Highly Destabilizing	0.525	D	0.507	neutral	None	None	None	None	N
L/C	0.5018	ambiguous	0.5524	ambiguous	-1.688	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	N
L/D	0.8534	likely_pathogenic	0.875	pathogenic	-2.633	Highly Destabilizing	0.842	D	0.638	neutral	None	None	None	None	N
L/E	0.4143	ambiguous	0.4497	ambiguous	-2.486	Highly Destabilizing	0.728	D	0.632	neutral	None	None	None	None	N
L/F	0.0965	likely_benign	0.1126	benign	-1.489	Destabilizing	0.728	D	0.537	neutral	None	None	None	None	N
L/G	0.6714	likely_pathogenic	0.6989	pathogenic	-2.861	Highly Destabilizing	0.728	D	0.609	neutral	None	None	None	None	N
L/H	0.1954	likely_benign	0.2262	benign	-2.249	Highly Destabilizing	0.037	N	0.483	neutral	None	None	None	None	N
L/I	0.1275	likely_benign	0.14	benign	-1.075	Destabilizing	0.915	D	0.486	neutral	None	None	None	None	N
L/K	0.214	likely_benign	0.2414	benign	-1.791	Destabilizing	0.728	D	0.583	neutral	None	None	None	None	N
L/M	0.0967	likely_benign	0.1066	benign	-0.99	Destabilizing	0.989	D	0.569	neutral	N	0.497268449	None	None	N
L/N	0.4935	ambiguous	0.5412	ambiguous	-1.936	Destabilizing	0.842	D	0.633	neutral	None	None	None	None	N
L/P	0.9814	likely_pathogenic	0.9802	pathogenic	-1.491	Destabilizing	0.966	D	0.654	neutral	N	0.497486939	None	None	N
L/Q	0.1129	likely_benign	0.1293	benign	-1.937	Destabilizing	0.267	N	0.441	neutral	N	0.512525903	None	None	N
L/R	0.1561	likely_benign	0.1677	benign	-1.352	Destabilizing	0.934	D	0.626	neutral	N	0.489553043	None	None	N
L/S	0.3722	ambiguous	0.4326	ambiguous	-2.591	Highly Destabilizing	0.067	N	0.444	neutral	None	None	None	None	N
L/T	0.2779	likely_benign	0.3198	benign	-2.319	Highly Destabilizing	0.728	D	0.545	neutral	None	None	None	None	N
L/V	0.1162	likely_benign	0.1301	benign	-1.491	Destabilizing	0.801	D	0.518	neutral	N	0.51389134	None	None	N
L/W	0.1769	likely_benign	0.1756	benign	-1.821	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
L/Y	0.2175	likely_benign	0.2485	benign	-1.554	Destabilizing	0.067	N	0.324	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.