TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17387	52384;52385;52386	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
N2AB	15746	47461;47462;47463	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
N2A	14819	44680;44681;44682	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
N2B	8322	25189;25190;25191	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
Novex-1	8447	25564;25565;25566	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
Novex-2	8514	25765;25766;25767	chr2:178608852;178608851;178608850	chr2:179473579;179473578;179473577
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-14
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.3245
• 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
L/H	rs2154197942	None	0.915	N	0.601	0.355	0.736726114388	gnomAD-4.0.0	1.36983E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79973E-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
L/A	0.2062	likely_benign	0.1772	benign	-2.106	Highly Destabilizing	0.035	N	0.42	neutral	None	None	None	None	N
L/C	0.3618	ambiguous	0.3252	benign	-1.446	Destabilizing	0.824	D	0.533	neutral	None	None	None	None	N
L/D	0.6311	likely_pathogenic	0.5954	pathogenic	-1.785	Destabilizing	0.38	N	0.609	neutral	None	None	None	None	N
L/E	0.3739	ambiguous	0.3582	ambiguous	-1.73	Destabilizing	0.38	N	0.602	neutral	None	None	None	None	N
L/F	0.1327	likely_benign	0.1171	benign	-1.423	Destabilizing	0.317	N	0.476	neutral	N	0.502781418	None	None	N
L/G	0.5087	ambiguous	0.4444	ambiguous	-2.484	Highly Destabilizing	0.149	N	0.581	neutral	None	None	None	None	N
L/H	0.1945	likely_benign	0.1713	benign	-1.652	Destabilizing	0.915	D	0.601	neutral	N	0.492564424	None	None	N
L/I	0.0654	likely_benign	0.0587	benign	-1.102	Destabilizing	None	N	0.197	neutral	N	0.44902429	None	None	N
L/K	0.2915	likely_benign	0.2791	benign	-1.502	Destabilizing	0.38	N	0.605	neutral	None	None	None	None	N
L/M	0.1027	likely_benign	0.089	benign	-0.936	Destabilizing	0.38	N	0.525	neutral	None	None	None	None	N
L/N	0.2537	likely_benign	0.223	benign	-1.43	Destabilizing	0.38	N	0.607	neutral	None	None	None	None	N
L/P	0.8954	likely_pathogenic	0.8831	pathogenic	-1.409	Destabilizing	0.484	N	0.607	neutral	N	0.466786882	None	None	N
L/Q	0.1507	likely_benign	0.1367	benign	-1.578	Destabilizing	0.555	D	0.599	neutral	None	None	None	None	N
L/R	0.2268	likely_benign	0.2082	benign	-0.913	Destabilizing	0.317	N	0.603	neutral	N	0.469687564	None	None	N
L/S	0.2042	likely_benign	0.1693	benign	-2.104	Highly Destabilizing	0.081	N	0.519	neutral	None	None	None	None	N
L/T	0.1111	likely_benign	0.1016	benign	-1.932	Destabilizing	0.001	N	0.293	neutral	None	None	None	None	N
L/V	0.0719	likely_benign	0.0637	benign	-1.409	Destabilizing	None	N	0.238	neutral	N	0.404809366	None	None	N
L/W	0.3126	likely_benign	0.2577	benign	-1.534	Destabilizing	0.935	D	0.597	neutral	None	None	None	None	N
L/Y	0.301	likely_benign	0.26	benign	-1.315	Destabilizing	0.555	D	0.563	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.