TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21974	66145;66146;66147	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
N2AB	20333	61222;61223;61224	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
N2A	19406	58441;58442;58443	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
N2B	12909	38950;38951;38952	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
Novex-1	13034	39325;39326;39327	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
Novex-2	13101	39526;39527;39528	chr2:178582536;178582535;178582534	chr2:179447263;179447262;179447261
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-47
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.3758
• 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
M/I	rs751625996	-0.378	0.101	N	0.275	0.193	0.365317461125	gnomAD-2.1.1	7.67E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.21931E-04	None	0	0	0
M/I	rs751625996	-0.378	0.101	N	0.275	0.193	0.365317461125	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
M/I	rs751625996	-0.378	0.101	N	0.275	0.193	0.365317461125	gnomAD-4.0.0	2.79036E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.94419E-04	0
M/R	rs373530806	0.117	0.213	N	0.437	0.319	0.388010793773	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
M/R	rs373530806	0.117	0.213	N	0.437	0.319	0.388010793773	gnomAD-4.0.0	1.36921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32035E-05	0
M/T	rs373530806	-0.51	0.183	N	0.388	0.304	0.438806408302	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
M/T	rs373530806	-0.51	0.183	N	0.388	0.304	0.438806408302	gnomAD-4.0.0	2.73842E-06	None	None	None	None	N	None	0	0	None	0	2.52653E-05	None	0	0	0	1.16017E-05	3.31576E-05
M/V	rs370691527	-0.679	0.001	N	0.191	0.271	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
M/V	rs370691527	-0.679	0.001	N	0.191	0.271	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
M/V	rs370691527	-0.679	0.001	N	0.191	0.271	None	gnomAD-4.0.0	8.68142E-06	None	None	None	None	N	None	2.67308E-05	0	None	0	2.23514E-05	None	0	0	7.63215E-06	0	3.20513E-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
M/A	0.3287	likely_benign	0.2717	benign	-2.11	Highly Destabilizing	0.061	N	0.306	neutral	None	None	None	None	N
M/C	0.63	likely_pathogenic	0.6131	pathogenic	-1.909	Destabilizing	0.94	D	0.511	neutral	None	None	None	None	N
M/D	0.7329	likely_pathogenic	0.7105	pathogenic	-1.233	Destabilizing	0.418	N	0.508	neutral	None	None	None	None	N
M/E	0.4555	ambiguous	0.4511	ambiguous	-1.134	Destabilizing	0.129	N	0.459	neutral	None	None	None	None	N
M/F	0.2634	likely_benign	0.2628	benign	-0.916	Destabilizing	0.418	N	0.375	neutral	None	None	None	None	N
M/G	0.6328	likely_pathogenic	0.5685	pathogenic	-2.498	Highly Destabilizing	0.418	N	0.501	neutral	None	None	None	None	N
M/H	0.3574	ambiguous	0.3588	ambiguous	-1.704	Destabilizing	0.836	D	0.559	neutral	None	None	None	None	N
M/I	0.2555	likely_benign	0.202	benign	-1.056	Destabilizing	0.101	N	0.275	neutral	N	0.403809289	None	None	N
M/K	0.2856	likely_benign	0.2557	benign	-0.963	Destabilizing	None	N	0.271	neutral	N	0.359365078	None	None	N
M/L	0.1286	likely_benign	0.1174	benign	-1.056	Destabilizing	None	N	0.187	neutral	N	0.377161405	None	None	N
M/N	0.3776	ambiguous	0.3399	benign	-0.972	Destabilizing	0.418	N	0.519	neutral	None	None	None	None	N
M/P	0.976	likely_pathogenic	0.9694	pathogenic	-1.382	Destabilizing	0.593	D	0.52	neutral	None	None	None	None	N
M/Q	0.2377	likely_benign	0.2277	benign	-0.949	Destabilizing	0.264	N	0.335	neutral	None	None	None	None	N
M/R	0.3198	likely_benign	0.2953	benign	-0.673	Destabilizing	0.213	N	0.437	neutral	N	0.402481137	None	None	N
M/S	0.2624	likely_benign	0.2338	benign	-1.635	Destabilizing	0.129	N	0.383	neutral	None	None	None	None	N
M/T	0.1286	likely_benign	0.1096	benign	-1.415	Destabilizing	0.183	N	0.388	neutral	N	0.300372703	None	None	N
M/V	0.0737	likely_benign	0.0629	benign	-1.382	Destabilizing	0.001	N	0.191	neutral	N	0.38410602	None	None	N
M/W	0.6082	likely_pathogenic	0.6274	pathogenic	-0.958	Destabilizing	0.983	D	0.503	neutral	None	None	None	None	N
M/Y	0.4717	ambiguous	0.4752	ambiguous	-0.97	Destabilizing	0.836	D	0.569	neutral	None	None	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.