TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2215	6868;6869;6870	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
N2AB	2215	6868;6869;6870	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
N2A	2215	6868;6869;6870	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
N2B	2169	6730;6731;6732	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
Novex-1	2169	6730;6731;6732	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
Novex-2	2169	6730;6731;6732	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793
Novex-3	2215	6868;6869;6870	chr2:178775068;178775067;178775066	chr2:179639795;179639794;179639793

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-11
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.8168
• 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
H/R	rs778552915	0.106	0.096	N	0.28	0.123	0.200317383148	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
H/R	rs778552915	0.106	0.096	N	0.28	0.123	0.200317383148	gnomAD-4.0.0	1.59074E-06	None	None	None	None	N	None	0	0	None	0	2.77562E-05	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	0.1241	likely_benign	0.115	benign	0.466	Stabilizing	0.025	N	0.264	neutral	None	None	None	None	N
H/C	0.1045	likely_benign	0.0993	benign	0.617	Stabilizing	0.958	D	0.295	neutral	None	None	None	None	N
H/D	0.138	likely_benign	0.1264	benign	-0.282	Destabilizing	0.042	N	0.325	neutral	N	0.491716332	None	None	N
H/E	0.1425	likely_benign	0.1309	benign	-0.269	Destabilizing	None	N	0.133	neutral	None	None	None	None	N
H/F	0.1318	likely_benign	0.128	benign	1.037	Stabilizing	None	N	0.113	neutral	None	None	None	None	N
H/G	0.1524	likely_benign	0.1444	benign	0.238	Stabilizing	0.055	N	0.339	neutral	None	None	None	None	N
H/I	0.1368	likely_benign	0.1289	benign	1.033	Stabilizing	0.22	N	0.429	neutral	None	None	None	None	N
H/K	0.1077	likely_benign	0.1037	benign	0.378	Stabilizing	0.055	N	0.323	neutral	None	None	None	None	N
H/L	0.0755	likely_benign	0.0732	benign	1.033	Stabilizing	0.042	N	0.285	neutral	N	0.484833154	None	None	N
H/M	0.2271	likely_benign	0.2112	benign	0.649	Stabilizing	0.667	D	0.329	neutral	None	None	None	None	N
H/N	0.0851	likely_benign	0.0815	benign	0.199	Stabilizing	0.042	N	0.273	neutral	N	0.503467543	None	None	N
H/P	0.1114	likely_benign	0.1075	benign	0.867	Stabilizing	0.301	N	0.391	neutral	N	0.477807057	None	None	N
H/Q	0.0934	likely_benign	0.0857	benign	0.278	Stabilizing	0.003	N	0.217	neutral	N	0.443189759	None	None	N
H/R	0.064	likely_benign	0.06	benign	-0.144	Destabilizing	0.096	N	0.28	neutral	N	0.451898078	None	None	N
H/S	0.1088	likely_benign	0.1057	benign	0.371	Stabilizing	0.002	N	0.145	neutral	None	None	None	None	N
H/T	0.1127	likely_benign	0.1022	benign	0.477	Stabilizing	0.055	N	0.342	neutral	None	None	None	None	N
H/V	0.1195	likely_benign	0.1114	benign	0.867	Stabilizing	0.104	N	0.363	neutral	None	None	None	None	N
H/W	0.2062	likely_benign	0.2001	benign	0.928	Stabilizing	0.667	D	0.311	neutral	None	None	None	None	N
H/Y	0.0736	likely_benign	0.0695	benign	1.178	Stabilizing	None	N	0.136	neutral	N	0.50932901	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.