TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25037	75334;75335;75336	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
N2AB	23396	70411;70412;70413	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
N2A	22469	67630;67631;67632	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
N2B	15972	48139;48140;48141	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
Novex-1	16097	48514;48515;48516	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
Novex-2	16164	48715;48716;48717	chr2:178571023;178571022;178571021	chr2:179435750;179435749;179435748
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: Fn3-70
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7814
• 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/M	None	None	0.999	N	0.624	0.377	0.240491677333	gnomAD-4.0.0	6.84696E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0015E-07	0	0
K/T	None	None	0.967	N	0.585	0.344	0.210429274316	gnomAD-4.0.0	1.36939E-06	None	None	None	None	I	None	0	2.23734E-05	None	0	0	None	0	0	9.0015E-07	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	0.4328	ambiguous	0.4117	ambiguous	-0.123	Destabilizing	0.916	D	0.587	neutral	None	None	None	None	I
K/C	0.7162	likely_pathogenic	0.7182	pathogenic	-0.18	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/D	0.7923	likely_pathogenic	0.7713	pathogenic	0.153	Stabilizing	0.987	D	0.587	neutral	None	None	None	None	I
K/E	0.3455	ambiguous	0.338	benign	0.156	Stabilizing	0.892	D	0.582	neutral	N	0.470038989	None	None	I
K/F	0.8509	likely_pathogenic	0.8449	pathogenic	-0.393	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	I
K/G	0.6445	likely_pathogenic	0.6292	pathogenic	-0.325	Destabilizing	0.975	D	0.537	neutral	None	None	None	None	I
K/H	0.4157	ambiguous	0.4054	ambiguous	-0.7	Destabilizing	0.999	D	0.624	neutral	None	None	None	None	I
K/I	0.4017	ambiguous	0.3806	ambiguous	0.33	Stabilizing	0.987	D	0.661	neutral	None	None	None	None	I
K/L	0.4111	ambiguous	0.4001	ambiguous	0.33	Stabilizing	0.975	D	0.536	neutral	None	None	None	None	I
K/M	0.2749	likely_benign	0.2674	benign	0.322	Stabilizing	0.999	D	0.624	neutral	N	0.507194655	None	None	I
K/N	0.6429	likely_pathogenic	0.6145	pathogenic	0.262	Stabilizing	0.983	D	0.683	prob.neutral	N	0.455372491	None	None	I
K/P	0.5623	ambiguous	0.5366	ambiguous	0.207	Stabilizing	0.033	N	0.434	neutral	None	None	None	None	I
K/Q	0.1829	likely_benign	0.1845	benign	0.031	Stabilizing	0.983	D	0.691	prob.neutral	N	0.510656247	None	None	I
K/R	0.0769	likely_benign	0.0798	benign	0.009	Stabilizing	0.944	D	0.555	neutral	N	0.475196879	None	None	I
K/S	0.5867	likely_pathogenic	0.5609	ambiguous	-0.299	Destabilizing	0.916	D	0.603	neutral	None	None	None	None	I
K/T	0.3095	likely_benign	0.2848	benign	-0.143	Destabilizing	0.967	D	0.585	neutral	N	0.484701797	None	None	I
K/V	0.3106	likely_benign	0.3058	benign	0.207	Stabilizing	0.987	D	0.597	neutral	None	None	None	None	I
K/W	0.8371	likely_pathogenic	0.8374	pathogenic	-0.355	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
K/Y	0.7427	likely_pathogenic	0.7321	pathogenic	0.009	Stabilizing	0.996	D	0.646	neutral	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.