TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30453	91582;91583;91584	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
N2AB	28812	86659;86660;86661	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
N2A	27885	83878;83879;83880	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
N2B	21388	64387;64388;64389	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
Novex-1	21513	64762;64763;64764	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
Novex-2	21580	64963;64964;64965	chr2:178551174;178551173;178551172	chr2:179415901;179415900;179415899
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: Fn3-110
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5735
• 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	None	None	0.997	N	0.622	0.405	0.343101102393	gnomAD-4.0.0	1.59177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8592E-06	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	0.583	likely_pathogenic	0.6495	pathogenic	-0.041	Destabilizing	0.983	D	0.605	neutral	None	None	None	None	I
K/C	0.8258	likely_pathogenic	0.8472	pathogenic	-0.22	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
K/D	0.8501	likely_pathogenic	0.8813	pathogenic	0.067	Stabilizing	0.998	D	0.666	neutral	None	None	None	None	I
K/E	0.4938	ambiguous	0.5593	ambiguous	0.085	Stabilizing	0.978	D	0.562	neutral	N	0.48923333	None	None	I
K/F	0.9269	likely_pathogenic	0.9436	pathogenic	-0.187	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
K/G	0.7554	likely_pathogenic	0.7971	pathogenic	-0.26	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
K/H	0.4951	ambiguous	0.5243	ambiguous	-0.509	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
K/I	0.6224	likely_pathogenic	0.6738	pathogenic	0.463	Stabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
K/L	0.5931	likely_pathogenic	0.6448	pathogenic	0.463	Stabilizing	0.995	D	0.575	neutral	None	None	None	None	I
K/M	0.4995	ambiguous	0.5528	ambiguous	0.231	Stabilizing	1.0	D	0.633	neutral	N	0.469851529	None	None	I
K/N	0.7465	likely_pathogenic	0.7974	pathogenic	0.169	Stabilizing	0.997	D	0.657	neutral	N	0.468584081	None	None	I
K/P	0.6608	likely_pathogenic	0.7247	pathogenic	0.324	Stabilizing	0.999	D	0.664	neutral	None	None	None	None	I
K/Q	0.2516	likely_benign	0.2775	benign	0.01	Stabilizing	0.994	D	0.669	neutral	N	0.518692232	None	None	I
K/R	0.082	likely_benign	0.0808	benign	-0.064	Destabilizing	0.121	N	0.208	neutral	N	0.470901073	None	None	I
K/S	0.7255	likely_pathogenic	0.7781	pathogenic	-0.333	Destabilizing	0.992	D	0.607	neutral	None	None	None	None	I
K/T	0.4464	ambiguous	0.5115	ambiguous	-0.159	Destabilizing	0.997	D	0.622	neutral	N	0.512323621	None	None	I
K/V	0.5013	ambiguous	0.5604	ambiguous	0.324	Stabilizing	0.998	D	0.672	neutral	None	None	None	None	I
K/W	0.9146	likely_pathogenic	0.9305	pathogenic	-0.19	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/Y	0.8485	likely_pathogenic	0.8762	pathogenic	0.154	Stabilizing	0.999	D	0.679	prob.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.