TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3215	9868;9869;9870	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
N2AB	3215	9868;9869;9870	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
N2A	3215	9868;9869;9870	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
N2B	3169	9730;9731;9732	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
Novex-1	3169	9730;9731;9732	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
Novex-2	3169	9730;9731;9732	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166
Novex-3	3215	9868;9869;9870	chr2:178766441;178766440;178766439	chr2:179631168;179631167;179631166

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-22
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.2502
• 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
A/P	None	None	0.999	D	0.861	0.659	0.516326692288	gnomAD-4.0.0	1.59051E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0217E-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
A/C	0.8002	likely_pathogenic	0.7962	pathogenic	-1.03	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
A/D	0.826	likely_pathogenic	0.8631	pathogenic	-0.804	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
A/E	0.5996	likely_pathogenic	0.5998	pathogenic	-0.837	Destabilizing	0.999	D	0.767	deleterious	N	0.498557583	None	None	N
A/F	0.7586	likely_pathogenic	0.7945	pathogenic	-1.057	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/G	0.3358	likely_benign	0.3406	ambiguous	-1.155	Destabilizing	0.996	D	0.521	neutral	D	0.567178943	None	None	N
A/H	0.8567	likely_pathogenic	0.8546	pathogenic	-1.216	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
A/I	0.6739	likely_pathogenic	0.7341	pathogenic	-0.375	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
A/K	0.8067	likely_pathogenic	0.8178	pathogenic	-1.03	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
A/L	0.6214	likely_pathogenic	0.6605	pathogenic	-0.375	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
A/M	0.5672	likely_pathogenic	0.6032	pathogenic	-0.367	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
A/N	0.731	likely_pathogenic	0.7501	pathogenic	-0.792	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
A/P	0.972	likely_pathogenic	0.9827	pathogenic	-0.51	Destabilizing	0.999	D	0.861	deleterious	D	0.650001637	None	None	N
A/Q	0.6423	likely_pathogenic	0.6121	pathogenic	-0.943	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/R	0.6718	likely_pathogenic	0.6825	pathogenic	-0.716	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
A/S	0.1275	likely_benign	0.1261	benign	-1.229	Destabilizing	0.957	D	0.325	neutral	N	0.506933316	None	None	N
A/T	0.2389	likely_benign	0.2758	benign	-1.155	Destabilizing	0.992	D	0.571	neutral	D	0.58262553	None	None	N
A/V	0.4148	ambiguous	0.4818	ambiguous	-0.51	Destabilizing	0.998	D	0.619	neutral	D	0.648369659	None	None	N
A/W	0.9629	likely_pathogenic	0.97	pathogenic	-1.339	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/Y	0.8664	likely_pathogenic	0.8761	pathogenic	-0.933	Destabilizing	1.0	D	0.875	deleterious	None	None	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.