TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5783	17572;17573;17574	chr2:178731419;178731418;178731417	chr2:179596146;179596145;179596144
N2AB	5466	16621;16622;16623	chr2:178731419;178731418;178731417	chr2:179596146;179596145;179596144
N2A	4539	13840;13841;13842	chr2:178731419;178731418;178731417	chr2:179596146;179596145;179596144
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-41
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3767
• 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/I	None	None	0.998	N	0.775	0.564	0.671502058982	gnomAD-4.0.0	6.84202E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87259E-05	0	0	0	0
N/S	None	None	0.961	D	0.553	0.26	0.330589388543	gnomAD-4.0.0	2.05261E-06	None	None	None	None	N	None	2.98846E-05	0	None	0	0	None	0	0	1.79892E-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	0.3977	ambiguous	0.3606	ambiguous	-0.816	Destabilizing	0.97	D	0.673	neutral	None	None	None	None	N
N/C	0.4891	ambiguous	0.451	ambiguous	0.008	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
N/D	0.14	likely_benign	0.1326	benign	-0.075	Destabilizing	0.961	D	0.581	neutral	N	0.516780583	None	None	N
N/E	0.5055	ambiguous	0.4589	ambiguous	0.036	Stabilizing	0.942	D	0.563	neutral	None	None	None	None	N
N/F	0.7686	likely_pathogenic	0.7416	pathogenic	-0.69	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
N/G	0.2835	likely_benign	0.2589	benign	-1.148	Destabilizing	0.092	N	0.258	neutral	None	None	None	None	N
N/H	0.1445	likely_benign	0.1351	benign	-0.78	Destabilizing	0.994	D	0.634	neutral	N	0.489455446	None	None	N
N/I	0.6599	likely_pathogenic	0.6226	pathogenic	0.025	Stabilizing	0.998	D	0.775	deleterious	N	0.493494371	None	None	N
N/K	0.4199	ambiguous	0.3651	ambiguous	0.028	Stabilizing	0.925	D	0.589	neutral	N	0.490541402	None	None	N
N/L	0.5059	ambiguous	0.4735	ambiguous	0.025	Stabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	N
N/M	0.5705	likely_pathogenic	0.5239	ambiguous	0.266	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
N/P	0.9081	likely_pathogenic	0.8938	pathogenic	-0.226	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
N/Q	0.4027	ambiguous	0.362	ambiguous	-0.531	Destabilizing	0.746	D	0.243	neutral	None	None	None	None	N
N/R	0.4194	ambiguous	0.3632	ambiguous	-0.04	Destabilizing	0.991	D	0.617	neutral	None	None	None	None	N
N/S	0.1072	likely_benign	0.1055	benign	-0.714	Destabilizing	0.961	D	0.553	neutral	D	0.532038037	None	None	N
N/T	0.272	likely_benign	0.2468	benign	-0.393	Destabilizing	0.98	D	0.597	neutral	D	0.524458704	None	None	N
N/V	0.6256	likely_pathogenic	0.5874	pathogenic	-0.226	Destabilizing	0.996	D	0.763	deleterious	None	None	None	None	N
N/W	0.8912	likely_pathogenic	0.8651	pathogenic	-0.474	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
N/Y	0.2961	likely_benign	0.2706	benign	-0.229	Destabilizing	0.998	D	0.762	deleterious	D	0.533598262	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.