TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19797	59614;59615;59616	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
N2AB	18156	54691;54692;54693	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
N2A	17229	51910;51911;51912	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
N2B	10732	32419;32420;32421	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
Novex-1	10857	32794;32795;32796	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
Novex-2	10924	32995;32996;32997	chr2:178592616;178592615;178592614	chr2:179457343;179457342;179457341
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-119
• Domain position: 8
• Structural Position: 14
• Q(SASA): 0.6679
• 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/Y	rs2050464910	None	0.001	N	0.125	0.094	0.18995819373	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
H/Y	rs2050464910	None	0.001	N	0.125	0.094	0.18995819373	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	2.41324E-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
H/A	0.4107	ambiguous	0.4715	ambiguous	-0.017	Destabilizing	0.055	N	0.252	neutral	None	None	None	None	I
H/C	0.2367	likely_benign	0.2684	benign	0.521	Stabilizing	0.958	D	0.276	neutral	None	None	None	None	I
H/D	0.469	ambiguous	0.5703	pathogenic	-0.205	Destabilizing	0.042	N	0.309	neutral	N	0.471104221	None	None	I
H/E	0.4266	ambiguous	0.5207	ambiguous	-0.145	Destabilizing	0.055	N	0.229	neutral	None	None	None	None	I
H/F	0.3437	ambiguous	0.3544	ambiguous	0.975	Stabilizing	0.124	N	0.378	neutral	None	None	None	None	I
H/G	0.5529	ambiguous	0.6211	pathogenic	-0.345	Destabilizing	0.104	N	0.277	neutral	None	None	None	None	I
H/I	0.2703	likely_benign	0.3074	benign	0.849	Stabilizing	0.497	N	0.407	neutral	None	None	None	None	I
H/K	0.3067	likely_benign	0.4011	ambiguous	-0.055	Destabilizing	0.002	N	0.12	neutral	None	None	None	None	I
H/L	0.1346	likely_benign	0.1451	benign	0.849	Stabilizing	0.042	N	0.347	neutral	N	0.437242364	None	None	I
H/M	0.4308	ambiguous	0.4487	ambiguous	0.564	Stabilizing	0.667	D	0.281	neutral	None	None	None	None	I
H/N	0.1557	likely_benign	0.153	benign	-0.145	Destabilizing	0.001	N	0.114	neutral	N	0.454038613	None	None	I
H/P	0.3212	likely_benign	0.3853	ambiguous	0.585	Stabilizing	0.301	N	0.373	neutral	N	0.482745367	None	None	I
H/Q	0.219	likely_benign	0.2541	benign	0.034	Stabilizing	0.003	N	0.151	neutral	N	0.473989811	None	None	I
H/R	0.1461	likely_benign	0.194	benign	-0.705	Destabilizing	0.042	N	0.213	neutral	N	0.442552183	None	None	I
H/S	0.3616	ambiguous	0.3967	ambiguous	-0.043	Destabilizing	0.055	N	0.295	neutral	None	None	None	None	I
H/T	0.3078	likely_benign	0.3547	ambiguous	0.122	Stabilizing	0.22	N	0.332	neutral	None	None	None	None	I
H/V	0.2149	likely_benign	0.2496	benign	0.585	Stabilizing	0.22	N	0.405	neutral	None	None	None	None	I
H/W	0.4209	ambiguous	0.4838	ambiguous	1.097	Stabilizing	0.883	D	0.269	neutral	None	None	None	None	I
H/Y	0.1198	likely_benign	0.1271	benign	1.259	Stabilizing	0.001	N	0.125	neutral	N	0.462004735	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.