TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5946	18061;18062;18063	chr2:178730697;178730696;178730695	chr2:179595424;179595423;179595422
N2AB	5629	17110;17111;17112	chr2:178730697;178730696;178730695	chr2:179595424;179595423;179595422
N2A	4702	14329;14330;14331	chr2:178730697;178730696;178730695	chr2:179595424;179595423;179595422
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-43
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.9359
• 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
H/L	None	None	0.005	N	0.139	0.287	0.503498835695	gnomAD-4.0.0	6.84283E-07	None	None	None	None	I	None	2.98846E-05	0	None	0	0	None	0	0	0	0	0
H/R	rs1417520677	None	0.986	N	0.466	0.398	0.307332253619	gnomAD-4.0.0	1.36857E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79909E-06	0	0
H/Y	rs1251182445	0.957	0.986	N	0.46	0.402	0.4744847356	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Y	rs1251182445	0.957	0.986	N	0.46	0.402	0.4744847356	gnomAD-4.0.0	2.73716E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7991E-06	2.31889E-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
H/A	0.3635	ambiguous	0.3509	ambiguous	0.275	Stabilizing	0.863	D	0.359	neutral	None	None	None	None	I
H/C	0.4135	ambiguous	0.4118	ambiguous	0.44	Stabilizing	0.999	D	0.417	neutral	None	None	None	None	I
H/D	0.3454	ambiguous	0.3525	ambiguous	-0.22	Destabilizing	0.986	D	0.513	neutral	N	0.479819705	None	None	I
H/E	0.4002	ambiguous	0.4012	ambiguous	-0.202	Destabilizing	0.99	D	0.417	neutral	None	None	None	None	I
H/F	0.4024	ambiguous	0.3751	ambiguous	0.907	Stabilizing	0.939	D	0.509	neutral	None	None	None	None	I
H/G	0.5081	ambiguous	0.5204	ambiguous	0.034	Stabilizing	0.99	D	0.461	neutral	None	None	None	None	I
H/I	0.3847	ambiguous	0.3798	ambiguous	0.88	Stabilizing	0.759	D	0.403	neutral	None	None	None	None	I
H/K	0.3778	ambiguous	0.3925	ambiguous	0.175	Stabilizing	0.99	D	0.471	neutral	None	None	None	None	I
H/L	0.1299	likely_benign	0.1249	benign	0.88	Stabilizing	0.005	N	0.139	neutral	N	0.393414229	None	None	I
H/M	0.5338	ambiguous	0.518	ambiguous	0.539	Stabilizing	0.982	D	0.439	neutral	None	None	None	None	I
H/N	0.1463	likely_benign	0.1418	benign	0.017	Stabilizing	0.986	D	0.494	neutral	N	0.474240527	None	None	I
H/P	0.1189	likely_benign	0.1271	benign	0.702	Stabilizing	0.996	D	0.464	neutral	N	0.297817974	None	None	I
H/Q	0.2393	likely_benign	0.2368	benign	0.109	Stabilizing	0.996	D	0.444	neutral	N	0.415616298	None	None	I
H/R	0.1913	likely_benign	0.208	benign	-0.314	Destabilizing	0.986	D	0.466	neutral	N	0.488151187	None	None	I
H/S	0.2738	likely_benign	0.27	benign	0.119	Stabilizing	0.969	D	0.468	neutral	None	None	None	None	I
H/T	0.3924	ambiguous	0.398	ambiguous	0.235	Stabilizing	0.939	D	0.439	neutral	None	None	None	None	I
H/V	0.3338	likely_benign	0.3287	benign	0.702	Stabilizing	0.079	N	0.171	neutral	None	None	None	None	I
H/W	0.5345	ambiguous	0.5464	ambiguous	0.853	Stabilizing	0.999	D	0.407	neutral	None	None	None	None	I
H/Y	0.123	likely_benign	0.1207	benign	1.085	Stabilizing	0.986	D	0.46	neutral	N	0.518031377	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.