TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6437	19534;19535;19536	chr2:178728617;178728616;178728615	chr2:179593344;179593343;179593342
N2AB	6120	18583;18584;18585	chr2:178728617;178728616;178728615	chr2:179593344;179593343;179593342
N2A	5193	15802;15803;15804	chr2:178728617;178728616;178728615	chr2:179593344;179593343;179593342
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-48
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.6532
• 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
N/Y	None	None	0.999	N	0.567	0.352	0.416328079214	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.592	likely_pathogenic	0.424	ambiguous	-0.056	Destabilizing	0.983	D	0.455	neutral	None	None	None	None	N
N/C	0.7477	likely_pathogenic	0.5954	pathogenic	0.108	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
N/D	0.1359	likely_benign	0.1008	benign	0.087	Stabilizing	0.117	N	0.241	neutral	N	0.450530508	None	None	N
N/E	0.5107	ambiguous	0.3464	ambiguous	0.026	Stabilizing	0.966	D	0.406	neutral	None	None	None	None	N
N/F	0.8835	likely_pathogenic	0.809	pathogenic	-0.657	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
N/G	0.3894	ambiguous	0.2916	benign	-0.15	Destabilizing	0.983	D	0.374	neutral	None	None	None	None	N
N/H	0.1917	likely_benign	0.1541	benign	-0.16	Destabilizing	0.999	D	0.547	neutral	N	0.472733186	None	None	N
N/I	0.8101	likely_pathogenic	0.6456	pathogenic	0.091	Stabilizing	0.997	D	0.618	neutral	N	0.497927785	None	None	N
N/K	0.408	ambiguous	0.2867	benign	0.089	Stabilizing	0.977	D	0.459	neutral	N	0.455083003	None	None	N
N/L	0.7221	likely_pathogenic	0.5742	pathogenic	0.091	Stabilizing	0.998	D	0.595	neutral	None	None	None	None	N
N/M	0.7034	likely_pathogenic	0.5677	pathogenic	0.088	Stabilizing	1.0	D	0.582	neutral	None	None	None	None	N
N/P	0.9538	likely_pathogenic	0.875	pathogenic	0.065	Stabilizing	0.998	D	0.543	neutral	None	None	None	None	N
N/Q	0.4764	ambiguous	0.3647	ambiguous	-0.304	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
N/R	0.5056	ambiguous	0.3746	ambiguous	0.153	Stabilizing	0.998	D	0.526	neutral	None	None	None	None	N
N/S	0.1945	likely_benign	0.1372	benign	-0.074	Destabilizing	0.977	D	0.383	neutral	N	0.455955149	None	None	N
N/T	0.4653	ambiguous	0.2969	benign	-0.022	Destabilizing	0.989	D	0.441	neutral	N	0.461692822	None	None	N
N/V	0.804	likely_pathogenic	0.634	pathogenic	0.065	Stabilizing	0.998	D	0.593	neutral	None	None	None	None	N
N/W	0.9108	likely_pathogenic	0.8503	pathogenic	-0.804	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
N/Y	0.3442	ambiguous	0.2647	benign	-0.472	Destabilizing	0.999	D	0.567	neutral	N	0.477354768	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.