TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30805	92638;92639;92640	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
N2AB	29164	87715;87716;87717	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
N2A	28237	84934;84935;84936	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
N2B	21740	65443;65444;65445	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
Novex-1	21865	65818;65819;65820	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
Novex-2	21932	66019;66020;66021	chr2:178549213;178549212;178549211	chr2:179413940;179413939;179413938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-112
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.6989
• 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
P/S	rs1698365968	None	0.698	N	0.691	0.291	0.272639205421	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1698365968	None	0.698	N	0.691	0.291	0.272639205421	gnomAD-4.0.0	6.57289E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.46985E-05	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
P/A	0.0934	likely_benign	0.0847	benign	-1.204	Destabilizing	0.014	N	0.415	neutral	N	0.470690429	None	None	I
P/C	0.5348	ambiguous	0.498	ambiguous	-0.665	Destabilizing	0.994	D	0.737	prob.delet.	None	None	None	None	I
P/D	0.4674	ambiguous	0.4257	ambiguous	-1.297	Destabilizing	0.754	D	0.685	prob.neutral	None	None	None	None	I
P/E	0.2575	likely_benign	0.221	benign	-1.389	Destabilizing	0.043	N	0.406	neutral	None	None	None	None	I
P/F	0.4421	ambiguous	0.4029	ambiguous	-1.232	Destabilizing	0.994	D	0.721	prob.delet.	None	None	None	None	I
P/G	0.3459	ambiguous	0.3108	benign	-1.413	Destabilizing	0.754	D	0.677	prob.neutral	None	None	None	None	I
P/H	0.221	likely_benign	0.2011	benign	-0.978	Destabilizing	0.992	D	0.705	prob.neutral	N	0.481096156	None	None	I
P/I	0.2992	likely_benign	0.2642	benign	-0.765	Destabilizing	0.956	D	0.727	prob.delet.	None	None	None	None	I
P/K	0.2222	likely_benign	0.1947	benign	-0.997	Destabilizing	0.754	D	0.677	prob.neutral	None	None	None	None	I
P/L	0.1124	likely_benign	0.1022	benign	-0.765	Destabilizing	0.89	D	0.671	neutral	N	0.49695431	None	None	I
P/M	0.2779	likely_benign	0.2496	benign	-0.437	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
P/N	0.3388	likely_benign	0.3103	benign	-0.641	Destabilizing	0.956	D	0.711	prob.delet.	None	None	None	None	I
P/Q	0.158	likely_benign	0.139	benign	-0.963	Destabilizing	0.915	D	0.685	prob.neutral	None	None	None	None	I
P/R	0.1696	likely_benign	0.1525	benign	-0.338	Destabilizing	0.942	D	0.715	prob.delet.	N	0.490700342	None	None	I
P/S	0.1636	likely_benign	0.1501	benign	-0.995	Destabilizing	0.698	D	0.691	prob.neutral	N	0.519060379	None	None	I
P/T	0.1286	likely_benign	0.1158	benign	-1.0	Destabilizing	0.942	D	0.674	neutral	N	0.499127824	None	None	I
P/V	0.2026	likely_benign	0.1788	benign	-0.877	Destabilizing	0.915	D	0.647	neutral	None	None	None	None	I
P/W	0.6629	likely_pathogenic	0.6185	pathogenic	-1.317	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
P/Y	0.4458	ambiguous	0.4026	ambiguous	-1.065	Destabilizing	0.998	D	0.731	prob.delet.	None	None	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.