TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27942	84049;84050;84051	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
N2AB	26301	79126;79127;79128	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
N2A	25374	76345;76346;76347	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
N2B	18877	56854;56855;56856	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
Novex-1	19002	57229;57230;57231	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
Novex-2	19069	57430;57431;57432	chr2:178562308;178562307;178562306	chr2:179427035;179427034;179427033
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-91
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.6409
• 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
K/T	rs1703962301	None	0.92	N	0.658	0.445	0.422160833541	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1703962301	None	0.92	N	0.658	0.445	0.422160833541	gnomAD-4.0.0	6.57134E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46981E-05	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
K/A	0.5156	ambiguous	0.59	pathogenic	0.066	Stabilizing	0.781	D	0.587	neutral	None	None	None	None	I
K/C	0.6928	likely_pathogenic	0.7838	pathogenic	-0.191	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	I
K/D	0.9202	likely_pathogenic	0.9413	pathogenic	-0.085	Destabilizing	0.962	D	0.659	neutral	None	None	None	None	I
K/E	0.5339	ambiguous	0.6331	pathogenic	-0.089	Destabilizing	0.766	D	0.601	neutral	N	0.506763085	None	None	I
K/F	0.8468	likely_pathogenic	0.9065	pathogenic	-0.188	Destabilizing	0.996	D	0.743	deleterious	None	None	None	None	I
K/G	0.7295	likely_pathogenic	0.7782	pathogenic	-0.106	Destabilizing	0.022	N	0.466	neutral	None	None	None	None	I
K/H	0.4393	ambiguous	0.5363	ambiguous	-0.298	Destabilizing	0.996	D	0.685	prob.neutral	None	None	None	None	I
K/I	0.4896	ambiguous	0.5997	pathogenic	0.438	Stabilizing	0.82	D	0.748	deleterious	None	None	None	None	I
K/L	0.5979	likely_pathogenic	0.6843	pathogenic	0.438	Stabilizing	0.599	D	0.659	neutral	None	None	None	None	I
K/M	0.3209	likely_benign	0.4064	ambiguous	0.163	Stabilizing	0.981	D	0.687	prob.neutral	N	0.473067532	None	None	I
K/N	0.6745	likely_pathogenic	0.7379	pathogenic	0.274	Stabilizing	0.95	D	0.672	neutral	D	0.523887408	None	None	I
K/P	0.9817	likely_pathogenic	0.9847	pathogenic	0.341	Stabilizing	0.994	D	0.684	prob.neutral	None	None	None	None	I
K/Q	0.2622	likely_benign	0.3359	benign	0.094	Stabilizing	0.934	D	0.683	prob.neutral	N	0.520116385	None	None	I
K/R	0.1075	likely_benign	0.1215	benign	0.04	Stabilizing	0.669	D	0.568	neutral	N	0.471800085	None	None	I
K/S	0.7034	likely_pathogenic	0.7602	pathogenic	-0.156	Destabilizing	0.877	D	0.628	neutral	None	None	None	None	I
K/T	0.4077	ambiguous	0.4672	ambiguous	-0.026	Destabilizing	0.92	D	0.658	neutral	N	0.472053574	None	None	I
K/V	0.4409	ambiguous	0.523	ambiguous	0.341	Stabilizing	0.663	D	0.709	prob.delet.	None	None	None	None	I
K/W	0.8773	likely_pathogenic	0.9226	pathogenic	-0.238	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
K/Y	0.7172	likely_pathogenic	0.798	pathogenic	0.118	Stabilizing	0.878	D	0.741	deleterious	None	None	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.