TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26956	81091;81092;81093	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
N2AB	25315	76168;76169;76170	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
N2A	24388	73387;73388;73389	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
N2B	17891	53896;53897;53898	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
Novex-1	18016	54271;54272;54273	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
Novex-2	18083	54472;54473;54474	chr2:178565266;178565265;178565264	chr2:179429993;179429992;179429991
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-139
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.302
• 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
N/D	None	None	0.996	D	0.532	0.569	0.311387274539	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88267E-05	0	0	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
N/A	0.9561	likely_pathogenic	0.9607	pathogenic	-0.411	Destabilizing	0.994	D	0.572	neutral	None	None	None	None	I
N/C	0.7998	likely_pathogenic	0.8323	pathogenic	0.006	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
N/D	0.9579	likely_pathogenic	0.9543	pathogenic	-1.577	Destabilizing	0.996	D	0.532	neutral	D	0.530698433	None	None	I
N/E	0.9971	likely_pathogenic	0.9973	pathogenic	-1.532	Destabilizing	0.997	D	0.569	neutral	None	None	None	None	I
N/F	0.9982	likely_pathogenic	0.9981	pathogenic	-0.654	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
N/G	0.9073	likely_pathogenic	0.9187	pathogenic	-0.66	Destabilizing	0.997	D	0.5	neutral	None	None	None	None	I
N/H	0.9336	likely_pathogenic	0.9366	pathogenic	-0.68	Destabilizing	1.0	D	0.664	neutral	D	0.529003367	None	None	I
N/I	0.9815	likely_pathogenic	0.9778	pathogenic	0.184	Stabilizing	0.999	D	0.689	prob.neutral	D	0.535840222	None	None	I
N/K	0.9982	likely_pathogenic	0.9981	pathogenic	-0.107	Destabilizing	0.996	D	0.581	neutral	D	0.546600643	None	None	I
N/L	0.9569	likely_pathogenic	0.959	pathogenic	0.184	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	I
N/M	0.9857	likely_pathogenic	0.9845	pathogenic	0.771	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	I
N/P	0.9962	likely_pathogenic	0.9954	pathogenic	0.014	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	I
N/Q	0.995	likely_pathogenic	0.9957	pathogenic	-1.065	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
N/R	0.9955	likely_pathogenic	0.996	pathogenic	0.071	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	I
N/S	0.3041	likely_benign	0.3364	benign	-0.631	Destabilizing	0.905	D	0.299	neutral	N	0.482613412	None	None	I
N/T	0.7929	likely_pathogenic	0.7924	pathogenic	-0.446	Destabilizing	0.992	D	0.557	neutral	D	0.539345714	None	None	I
N/V	0.9559	likely_pathogenic	0.959	pathogenic	0.014	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
N/W	0.9996	likely_pathogenic	0.9996	pathogenic	-0.579	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
N/Y	0.9849	likely_pathogenic	0.9847	pathogenic	-0.222	Destabilizing	1.0	D	0.68	prob.neutral	D	0.558463927	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.