TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28881	86866;86867;86868	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
N2AB	27240	81943;81944;81945	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
N2A	26313	79162;79163;79164	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
N2B	19816	59671;59672;59673	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
Novex-1	19941	60046;60047;60048	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
Novex-2	20008	60247;60248;60249	chr2:178559491;178559490;178559489	chr2:179424218;179424217;179424216
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: Fn3-98
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2105
• 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/D	None	None	0.351	N	0.572	0.314	0.18274738541	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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	0.3418	ambiguous	0.4085	ambiguous	-1.247	Destabilizing	0.061	N	0.539	neutral	None	None	None	None	N
H/C	0.1271	likely_benign	0.1439	benign	-0.961	Destabilizing	0.94	D	0.624	neutral	None	None	None	None	N
H/D	0.4412	ambiguous	0.4882	ambiguous	-1.301	Destabilizing	0.351	N	0.572	neutral	N	0.442788964	None	None	N
H/E	0.4099	ambiguous	0.4453	ambiguous	-1.213	Destabilizing	0.418	N	0.41	neutral	None	None	None	None	N
H/F	0.2022	likely_benign	0.236	benign	-0.311	Destabilizing	0.264	N	0.553	neutral	None	None	None	None	N
H/G	0.5147	ambiguous	0.5786	pathogenic	-1.55	Destabilizing	0.418	N	0.565	neutral	None	None	None	None	N
H/I	0.1418	likely_benign	0.1796	benign	-0.407	Destabilizing	0.001	N	0.555	neutral	None	None	None	None	N
H/K	0.2953	likely_benign	0.33	benign	-1.273	Destabilizing	0.418	N	0.553	neutral	None	None	None	None	N
H/L	0.0954	likely_benign	0.1078	benign	-0.407	Destabilizing	None	N	0.535	neutral	N	0.346089137	None	None	N
H/M	0.362	ambiguous	0.4366	ambiguous	-0.609	Destabilizing	0.716	D	0.618	neutral	None	None	None	None	N
H/N	0.1401	likely_benign	0.1629	benign	-1.323	Destabilizing	0.351	N	0.489	neutral	N	0.403385214	None	None	N
H/P	0.8922	likely_pathogenic	0.9177	pathogenic	-0.67	Destabilizing	0.523	D	0.629	neutral	N	0.481173994	None	None	N
H/Q	0.1885	likely_benign	0.2136	benign	-1.121	Destabilizing	0.523	D	0.539	neutral	N	0.410657903	None	None	N
H/R	0.117	likely_benign	0.1219	benign	-1.309	Destabilizing	0.351	N	0.509	neutral	N	0.37550518	None	None	N
H/S	0.2782	likely_benign	0.3348	benign	-1.457	Destabilizing	0.129	N	0.493	neutral	None	None	None	None	N
H/T	0.2502	likely_benign	0.3034	benign	-1.28	Destabilizing	0.001	N	0.45	neutral	None	None	None	None	N
H/V	0.1398	likely_benign	0.1744	benign	-0.67	Destabilizing	0.001	N	0.552	neutral	None	None	None	None	N
H/W	0.3456	ambiguous	0.3905	ambiguous	-0.128	Destabilizing	0.951	D	0.607	neutral	None	None	None	None	N
H/Y	0.0814	likely_benign	0.0876	benign	0.069	Stabilizing	0.002	N	0.207	neutral	N	0.393016292	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.