TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14485	43678;43679;43680	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
N2AB	12844	38755;38756;38757	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
N2A	11917	35974;35975;35976	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
N2B	5420	16483;16484;16485	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
Novex-1	5545	16858;16859;16860	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
Novex-2	5612	17059;17060;17061	chr2:178632553;178632552;178632551	chr2:179497280;179497279;179497278
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-95
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.8511
• 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/Q	rs769249986	0.707	0.117	N	0.603	0.14	0.101711395817	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.55E-05	None	0	0	0
H/Q	rs769249986	0.707	0.117	N	0.603	0.14	0.101711395817	gnomAD-4.0.0	2.05328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.48044E-05	0
H/R	rs2059936761	None	None	N	0.286	0.174	0.0806252709748	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02737E-05

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	0.355	ambiguous	0.3238	benign	-0.24	Destabilizing	0.067	N	0.614	neutral	None	None	None	None	N
H/C	0.153	likely_benign	0.1409	benign	0.392	Stabilizing	0.935	D	0.61	neutral	None	None	None	None	N
H/D	0.3777	ambiguous	0.3482	ambiguous	-0.187	Destabilizing	0.117	N	0.637	neutral	N	0.480239083	None	None	N
H/E	0.3565	ambiguous	0.3238	benign	-0.121	Destabilizing	0.035	N	0.607	neutral	None	None	None	None	N
H/F	0.371	ambiguous	0.3381	benign	0.754	Stabilizing	0.555	D	0.651	neutral	None	None	None	None	N
H/G	0.3665	ambiguous	0.3471	ambiguous	-0.575	Destabilizing	0.149	N	0.631	neutral	None	None	None	None	N
H/I	0.3231	likely_benign	0.3013	benign	0.654	Stabilizing	0.555	D	0.648	neutral	None	None	None	None	N
H/K	0.1789	likely_benign	0.1706	benign	-0.14	Destabilizing	0.035	N	0.527	neutral	None	None	None	None	N
H/L	0.1392	likely_benign	0.1361	benign	0.654	Stabilizing	0.117	N	0.65	neutral	N	0.464663284	None	None	N
H/M	0.5052	ambiguous	0.4638	ambiguous	0.436	Stabilizing	0.791	D	0.627	neutral	None	None	None	None	N
H/N	0.1578	likely_benign	0.1484	benign	-0.218	Destabilizing	0.117	N	0.563	neutral	N	0.436709438	None	None	N
H/P	0.3791	ambiguous	0.4007	ambiguous	0.38	Stabilizing	0.484	N	0.648	neutral	N	0.48031287	None	None	N
H/Q	0.1509	likely_benign	0.1343	benign	-0.046	Destabilizing	0.117	N	0.603	neutral	N	0.390387439	None	None	N
H/R	0.0584	likely_benign	0.0586	benign	-0.679	Destabilizing	None	N	0.286	neutral	N	0.319195944	None	None	N
H/S	0.3049	likely_benign	0.2719	benign	-0.195	Destabilizing	0.149	N	0.607	neutral	None	None	None	None	N
H/T	0.3093	likely_benign	0.2778	benign	-0.022	Destabilizing	0.149	N	0.642	neutral	None	None	None	None	N
H/V	0.2696	likely_benign	0.2582	benign	0.38	Stabilizing	0.149	N	0.653	neutral	None	None	None	None	N
H/W	0.3101	likely_benign	0.3055	benign	0.937	Stabilizing	0.935	D	0.627	neutral	None	None	None	None	N
H/Y	0.1158	likely_benign	0.1116	benign	1.096	Stabilizing	0.211	N	0.604	neutral	N	0.480301101	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.