TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26046	78361;78362;78363	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
N2AB	24405	73438;73439;73440	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
N2A	23478	70657;70658;70659	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
N2B	16981	51166;51167;51168	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
Novex-1	17106	51541;51542;51543	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
Novex-2	17173	51742;51743;51744	chr2:178567996;178567995;178567994	chr2:179432723;179432722;179432721
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: Fn3-77
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.6193
• 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/N	rs747097682	-0.336	0.285	N	0.169	0.363	0.180583059064	gnomAD-2.1.1	3.63E-05	None	None	None	None	I	None	0	2.32194E-04	None	0	0	None	0	None	4.65E-05	0	0
H/N	rs747097682	-0.336	0.285	N	0.169	0.363	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
H/N	rs747097682	-0.336	0.285	N	0.169	0.363	0.180583059064	gnomAD-4.0.0	1.28176E-05	None	None	None	None	I	None	0	1.69601E-04	None	0	0	None	0	0	0	0	0
H/R	rs780141110	-0.58	0.166	N	0.161	0.13	None	gnomAD-2.1.1	7.16E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
H/R	rs780141110	-0.58	0.166	N	0.161	0.13	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
H/R	rs780141110	-0.58	0.166	N	0.161	0.13	None	gnomAD-4.0.0	3.04495E-06	None	None	None	None	I	None	3.4943E-05	0	None	0	0	None	0	0	1.20496E-06	0	0
H/Y	rs747097682	1.071	0.856	N	0.224	0.354	0.257292322809	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/Y	rs747097682	1.071	0.856	N	0.224	0.354	0.257292322809	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Y	rs747097682	1.071	0.856	N	0.224	0.354	0.257292322809	gnomAD-4.0.0	3.84526E-06	None	None	None	None	I	None	0	1.69601E-05	None	0	0	None	0	0	2.39415E-06	1.34037E-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	0.109	likely_benign	0.1104	benign	0.101	Stabilizing	0.187	N	0.212	neutral	None	None	None	None	I
H/C	0.1032	likely_benign	0.105	benign	0.487	Stabilizing	0.991	D	0.286	neutral	None	None	None	None	I
H/D	0.1671	likely_benign	0.1819	benign	-0.186	Destabilizing	0.285	N	0.218	neutral	N	0.382415296	None	None	I
H/E	0.1728	likely_benign	0.1877	benign	-0.152	Destabilizing	0.103	N	0.096	neutral	None	None	None	None	I
H/F	0.247	likely_benign	0.2579	benign	0.9	Stabilizing	0.965	D	0.353	neutral	None	None	None	None	I
H/G	0.1379	likely_benign	0.1432	benign	-0.18	Destabilizing	0.345	N	0.199	neutral	None	None	None	None	I
H/I	0.1896	likely_benign	0.2092	benign	0.824	Stabilizing	0.722	D	0.392	neutral	None	None	None	None	I
H/K	0.118	likely_benign	0.1217	benign	0.004	Stabilizing	0.209	N	0.213	neutral	None	None	None	None	I
H/L	0.0812	likely_benign	0.081	benign	0.824	Stabilizing	0.285	N	0.268	neutral	N	0.407753671	None	None	I
H/M	0.26	likely_benign	0.2735	benign	0.543	Stabilizing	0.901	D	0.302	neutral	None	None	None	None	I
H/N	0.0723	likely_benign	0.0727	benign	-0.103	Destabilizing	0.285	N	0.169	neutral	N	0.410063258	None	None	I
H/P	0.0709	likely_benign	0.071	benign	0.607	Stabilizing	None	N	0.113	neutral	N	0.35630613	None	None	I
H/Q	0.0804	likely_benign	0.082	benign	0.024	Stabilizing	0.002	N	0.069	neutral	N	0.371408869	None	None	I
H/R	0.0621	likely_benign	0.0647	benign	-0.55	Destabilizing	0.166	N	0.161	neutral	N	0.374083815	None	None	I
H/S	0.0994	likely_benign	0.1026	benign	0.004	Stabilizing	0.345	N	0.204	neutral	None	None	None	None	I
H/T	0.0989	likely_benign	0.1055	benign	0.136	Stabilizing	0.345	N	0.243	neutral	None	None	None	None	I
H/V	0.1384	likely_benign	0.1503	benign	0.607	Stabilizing	0.517	D	0.316	neutral	None	None	None	None	I
H/W	0.3204	likely_benign	0.3343	benign	0.937	Stabilizing	0.991	D	0.28	neutral	None	None	None	None	I
H/Y	0.0934	likely_benign	0.0948	benign	1.136	Stabilizing	0.856	D	0.224	neutral	N	0.470746357	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.