TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7388	22387;22388;22389	chr2:178722737;178722736;178722735	chr2:179587464;179587463;179587462
N2AB	7071	21436;21437;21438	chr2:178722737;178722736;178722735	chr2:179587464;179587463;179587462
N2A	6144	18655;18656;18657	chr2:178722737;178722736;178722735	chr2:179587464;179587463;179587462
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-58
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.8635
• 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/K	None	None	0.096	N	0.122	0.081	0.0482279557977	gnomAD-4.0.0	6.8448E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99675E-07	0	0
N/S	rs1350328102	0.488	None	N	0.097	0.066	0.0297737177859	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
N/S	rs1350328102	0.488	None	N	0.097	0.066	0.0297737177859	gnomAD-4.0.0	1.36894E-05	None	None	None	None	I	None	5.97943E-05	0	None	0	0	None	0	0	1.52944E-05	0	1.65804E-05

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	0.0978	likely_benign	0.1271	benign	-0.211	Destabilizing	0.025	N	0.211	neutral	None	None	None	None	I
N/C	0.1692	likely_benign	0.2618	benign	0.37	Stabilizing	0.883	D	0.195	neutral	None	None	None	None	I
N/D	0.0884	likely_benign	0.1082	benign	0.16	Stabilizing	0.081	N	0.126	neutral	N	0.386500459	None	None	I
N/E	0.2073	likely_benign	0.2691	benign	0.107	Stabilizing	0.124	N	0.119	neutral	None	None	None	None	I
N/F	0.2505	likely_benign	0.3233	benign	-0.711	Destabilizing	0.001	N	0.176	neutral	None	None	None	None	I
N/G	0.1065	likely_benign	0.1478	benign	-0.343	Destabilizing	None	N	0.097	neutral	None	None	None	None	I
N/H	0.0716	likely_benign	0.086	benign	-0.381	Destabilizing	0.602	D	0.232	neutral	N	0.452688166	None	None	I
N/I	0.1251	likely_benign	0.1588	benign	0.042	Stabilizing	0.096	N	0.286	neutral	N	0.490475763	None	None	I
N/K	0.1557	likely_benign	0.2111	benign	0.182	Stabilizing	0.096	N	0.122	neutral	N	0.399392399	None	None	I
N/L	0.1191	likely_benign	0.1478	benign	0.042	Stabilizing	0.055	N	0.231	neutral	None	None	None	None	I
N/M	0.1797	likely_benign	0.2254	benign	0.317	Stabilizing	0.667	D	0.205	neutral	None	None	None	None	I
N/P	0.264	likely_benign	0.3964	ambiguous	-0.018	Destabilizing	0.22	N	0.291	neutral	None	None	None	None	I
N/Q	0.1672	likely_benign	0.2198	benign	-0.207	Destabilizing	0.497	N	0.204	neutral	None	None	None	None	I
N/R	0.1512	likely_benign	0.2192	benign	0.254	Stabilizing	0.22	N	0.189	neutral	None	None	None	None	I
N/S	0.0517	likely_benign	0.0584	benign	0.016	Stabilizing	None	N	0.097	neutral	N	0.346056559	None	None	I
N/T	0.0707	likely_benign	0.0862	benign	0.092	Stabilizing	0.003	N	0.144	neutral	N	0.422191901	None	None	I
N/V	0.1357	likely_benign	0.1778	benign	-0.018	Destabilizing	0.004	N	0.195	neutral	None	None	None	None	I
N/W	0.4053	ambiguous	0.5592	ambiguous	-0.77	Destabilizing	0.958	D	0.203	neutral	None	None	None	None	I
N/Y	0.099	likely_benign	0.1269	benign	-0.473	Destabilizing	0.272	N	0.267	neutral	N	0.464078596	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.