TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6561	19906;19907;19908	chr2:178728143;178728142;178728141	chr2:179592870;179592869;179592868
N2AB	6244	18955;18956;18957	chr2:178728143;178728142;178728141	chr2:179592870;179592869;179592868
N2A	5317	16174;16175;16176	chr2:178728143;178728142;178728141	chr2:179592870;179592869;179592868
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-49
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6172
• 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
D/N	rs938213426	None	0.001	N	0.127	0.122	0.270001397563	gnomAD-4.0.0	2.06911E-06	None	None	None	None	N	None	0	2.2749E-05	None	0	0	None	0	0	9.04897E-07	0	1.67023E-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
D/A	0.0961	likely_benign	0.1003	benign	-0.174	Destabilizing	0.047	N	0.516	neutral	N	0.432220546	None	None	N
D/C	0.3324	likely_benign	0.3795	ambiguous	0.2	Stabilizing	0.983	D	0.574	neutral	None	None	None	None	N
D/E	0.1169	likely_benign	0.1183	benign	-0.282	Destabilizing	0.183	N	0.395	neutral	N	0.412285204	None	None	N
D/F	0.3208	likely_benign	0.325	benign	-0.278	Destabilizing	0.836	D	0.589	neutral	None	None	None	None	N
D/G	0.1065	likely_benign	0.1157	benign	-0.347	Destabilizing	0.101	N	0.477	neutral	N	0.477974266	None	None	N
D/H	0.1272	likely_benign	0.137	benign	-0.159	Destabilizing	0.794	D	0.537	neutral	N	0.445459202	None	None	N
D/I	0.1817	likely_benign	0.1847	benign	0.223	Stabilizing	0.01	N	0.418	neutral	None	None	None	None	N
D/K	0.1695	likely_benign	0.1767	benign	0.437	Stabilizing	0.264	N	0.519	neutral	None	None	None	None	N
D/L	0.2155	likely_benign	0.2201	benign	0.223	Stabilizing	0.129	N	0.646	neutral	None	None	None	None	N
D/M	0.3631	ambiguous	0.3717	ambiguous	0.39	Stabilizing	0.836	D	0.582	neutral	None	None	None	None	N
D/N	0.0675	likely_benign	0.0703	benign	0.249	Stabilizing	0.001	N	0.127	neutral	N	0.447998075	None	None	N
D/P	0.6764	likely_pathogenic	0.702	pathogenic	0.112	Stabilizing	0.593	D	0.537	neutral	None	None	None	None	N
D/Q	0.1701	likely_benign	0.1786	benign	0.251	Stabilizing	0.418	N	0.423	neutral	None	None	None	None	N
D/R	0.1783	likely_benign	0.1863	benign	0.514	Stabilizing	0.418	N	0.575	neutral	None	None	None	None	N
D/S	0.0635	likely_benign	0.0708	benign	0.137	Stabilizing	0.001	N	0.143	neutral	None	None	None	None	N
D/T	0.107	likely_benign	0.1188	benign	0.267	Stabilizing	0.129	N	0.541	neutral	None	None	None	None	N
D/V	0.1119	likely_benign	0.1159	benign	0.112	Stabilizing	0.101	N	0.64	neutral	N	0.44403505	None	None	N
D/W	0.6712	likely_pathogenic	0.6767	pathogenic	-0.204	Destabilizing	0.983	D	0.594	neutral	None	None	None	None	N
D/Y	0.1178	likely_benign	0.1192	benign	-0.047	Destabilizing	0.921	D	0.586	neutral	N	0.472299087	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.