TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7181	21766;21767;21768	chr2:178723559;178723558;178723557	chr2:179588286;179588285;179588284
N2AB	6864	20815;20816;20817	chr2:178723559;178723558;178723557	chr2:179588286;179588285;179588284
N2A	5937	18034;18035;18036	chr2:178723559;178723558;178723557	chr2:179588286;179588285;179588284
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: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-56
• Domain position: 45
• Structural Position: 102
• Q(SASA): 1.0978
• 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/G	None	None	0.012	N	0.341	0.173	0.134241683229	gnomAD-4.0.0	3.18433E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71932E-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
D/A	0.1239	likely_benign	0.1284	benign	0.067	Stabilizing	None	N	0.195	neutral	N	0.459864855	None	None	N
D/C	0.4995	ambiguous	0.5459	ambiguous	-0.21	Destabilizing	0.864	D	0.296	neutral	None	None	None	None	N
D/E	0.1089	likely_benign	0.1151	benign	-0.322	Destabilizing	None	N	0.17	neutral	N	0.455688399	None	None	N
D/F	0.4112	ambiguous	0.4308	ambiguous	-0.048	Destabilizing	0.628	D	0.312	neutral	None	None	None	None	N
D/G	0.1128	likely_benign	0.1216	benign	-0.022	Destabilizing	0.012	N	0.341	neutral	N	0.473042009	None	None	N
D/H	0.1761	likely_benign	0.1901	benign	0.604	Stabilizing	0.171	N	0.304	neutral	N	0.494401503	None	None	N
D/I	0.2461	likely_benign	0.2624	benign	0.233	Stabilizing	0.356	N	0.363	neutral	None	None	None	None	N
D/K	0.1849	likely_benign	0.1952	benign	0.379	Stabilizing	0.016	N	0.343	neutral	None	None	None	None	N
D/L	0.2462	likely_benign	0.2586	benign	0.233	Stabilizing	0.072	N	0.378	neutral	None	None	None	None	N
D/M	0.4638	ambiguous	0.4854	ambiguous	-0.009	Destabilizing	0.864	D	0.294	neutral	None	None	None	None	N
D/N	0.0854	likely_benign	0.0879	benign	0.176	Stabilizing	None	N	0.165	neutral	N	0.49137984	None	None	N
D/P	0.2906	likely_benign	0.3122	benign	0.195	Stabilizing	None	N	0.245	neutral	None	None	None	None	N
D/Q	0.1925	likely_benign	0.2051	benign	0.175	Stabilizing	0.038	N	0.298	neutral	None	None	None	None	N
D/R	0.1932	likely_benign	0.2081	benign	0.599	Stabilizing	None	N	0.275	neutral	None	None	None	None	N
D/S	0.0921	likely_benign	0.096	benign	0.074	Stabilizing	0.016	N	0.295	neutral	None	None	None	None	N
D/T	0.1846	likely_benign	0.1909	benign	0.154	Stabilizing	0.038	N	0.346	neutral	None	None	None	None	N
D/V	0.1511	likely_benign	0.1612	benign	0.195	Stabilizing	0.055	N	0.395	neutral	N	0.507408085	None	None	N
D/W	0.6972	likely_pathogenic	0.7236	pathogenic	-0.031	Destabilizing	0.864	D	0.372	neutral	None	None	None	None	N
D/Y	0.164	likely_benign	0.1772	benign	0.168	Stabilizing	0.56	D	0.313	neutral	N	0.480748583	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.