TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23658	71197;71198;71199	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
N2AB	22017	66274;66275;66276	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
N2A	21090	63493;63494;63495	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
N2B	14593	44002;44003;44004	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
Novex-1	14718	44377;44378;44379	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
Novex-2	14785	44578;44579;44580	chr2:178575160;178575159;178575158	chr2:179439887;179439886;179439885
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-130
• Domain position: 22
• Structural Position: 38
• Q(SASA): 1.0084
• 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/F	None	None	1.0	N	0.657	0.25	0.658123265804	gnomAD-4.0.0	1.59389E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43538E-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	0.1684	likely_benign	0.1738	benign	-0.519	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	I
L/C	0.4316	ambiguous	0.4432	ambiguous	-0.916	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
L/D	0.6036	likely_pathogenic	0.6508	pathogenic	-0.355	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	I
L/E	0.3011	likely_benign	0.3373	benign	-0.444	Destabilizing	0.91	D	0.451	neutral	None	None	None	None	I
L/F	0.1156	likely_benign	0.1106	benign	-0.742	Destabilizing	1.0	D	0.657	neutral	N	0.469720142	None	None	I
L/G	0.448	ambiguous	0.4758	ambiguous	-0.587	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	I
L/H	0.1568	likely_benign	0.1661	benign	0.004	Stabilizing	1.0	D	0.669	neutral	N	0.478878343	None	None	I
L/I	0.0957	likely_benign	0.0885	benign	-0.45	Destabilizing	0.999	D	0.513	neutral	N	0.452153101	None	None	I
L/K	0.1763	likely_benign	0.197	benign	-0.444	Destabilizing	0.999	D	0.553	neutral	None	None	None	None	I
L/M	0.0992	likely_benign	0.0973	benign	-0.766	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
L/N	0.2933	likely_benign	0.3002	benign	-0.33	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	I
L/P	0.8091	likely_pathogenic	0.8245	pathogenic	-0.45	Destabilizing	1.0	D	0.668	neutral	N	0.484958768	None	None	I
L/Q	0.1185	likely_benign	0.1263	benign	-0.49	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	I
L/R	0.1384	likely_benign	0.1443	benign	-0.02	Destabilizing	0.999	D	0.629	neutral	N	0.43887716	None	None	I
L/S	0.1896	likely_benign	0.201	benign	-0.684	Destabilizing	0.999	D	0.556	neutral	None	None	None	None	I
L/T	0.1372	likely_benign	0.1434	benign	-0.683	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	I
L/V	0.0947	likely_benign	0.0936	benign	-0.45	Destabilizing	0.998	D	0.505	neutral	N	0.438493158	None	None	I
L/W	0.2	likely_benign	0.2018	benign	-0.75	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
L/Y	0.2624	likely_benign	0.2677	benign	-0.542	Destabilizing	1.0	D	0.68	prob.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.