TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3982	12169;12170;12171	chr2:178741289;178741288;178741287	chr2:179606016;179606015;179606014
N2AB	3665	11218;11219;11220	chr2:178741289;178741288;178741287	chr2:179606016;179606015;179606014
N2A	None	None	chr2:None	chr2:None
N2B	3619	11080;11081;11082	chr2:178741289;178741288;178741287	chr2:179606016;179606015;179606014
Novex-1	3744	11455;11456;11457	chr2:178741289;178741288;178741287	chr2:179606016;179606015;179606014
Novex-2	3811	11656;11657;11658	chr2:178741289;178741288;178741287	chr2:179606016;179606015;179606014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-28
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.9085
• 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
V/I	rs1032555583	None	0.001	N	0.148	0.112	None	gnomAD-4.0.0	4.10507E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.3966E-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
V/A	0.2106	likely_benign	0.1947	benign	-0.446	Destabilizing	None	N	0.091	neutral	N	0.436690744	None	None	I
V/C	0.7608	likely_pathogenic	0.7201	pathogenic	-0.827	Destabilizing	0.667	D	0.177	neutral	None	None	None	None	I
V/D	0.3381	likely_benign	0.3184	benign	-0.116	Destabilizing	0.042	N	0.227	neutral	N	0.423114327	None	None	I
V/E	0.3376	likely_benign	0.3121	benign	-0.205	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
V/F	0.2061	likely_benign	0.1809	benign	-0.624	Destabilizing	0.427	N	0.249	neutral	N	0.446379075	None	None	I
V/G	0.267	likely_benign	0.2428	benign	-0.556	Destabilizing	0.042	N	0.209	neutral	N	0.414071996	None	None	I
V/H	0.6424	likely_pathogenic	0.6019	pathogenic	0.006	Stabilizing	0.667	D	0.177	neutral	None	None	None	None	I
V/I	0.0756	likely_benign	0.0715	benign	-0.293	Destabilizing	0.001	N	0.148	neutral	N	0.447356772	None	None	I
V/K	0.4114	ambiguous	0.4094	ambiguous	-0.39	Destabilizing	0.055	N	0.186	neutral	None	None	None	None	I
V/L	0.2533	likely_benign	0.212	benign	-0.293	Destabilizing	0.007	N	0.145	neutral	N	0.447128882	None	None	I
V/M	0.1805	likely_benign	0.16	benign	-0.576	Destabilizing	0.497	N	0.161	neutral	None	None	None	None	I
V/N	0.2973	likely_benign	0.2741	benign	-0.263	Destabilizing	0.22	N	0.246	neutral	None	None	None	None	I
V/P	0.4059	ambiguous	0.3758	ambiguous	-0.313	Destabilizing	0.364	N	0.261	neutral	None	None	None	None	I
V/Q	0.427	ambiguous	0.405	ambiguous	-0.422	Destabilizing	0.004	N	0.182	neutral	None	None	None	None	I
V/R	0.3235	likely_benign	0.332	benign	0.057	Stabilizing	None	N	0.139	neutral	None	None	None	None	I
V/S	0.2458	likely_benign	0.2308	benign	-0.647	Destabilizing	0.055	N	0.175	neutral	None	None	None	None	I
V/T	0.2358	likely_benign	0.2212	benign	-0.629	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
V/W	0.8447	likely_pathogenic	0.8042	pathogenic	-0.684	Destabilizing	0.958	D	0.177	neutral	None	None	None	None	I
V/Y	0.5825	likely_pathogenic	0.5551	ambiguous	-0.415	Destabilizing	0.667	D	0.245	neutral	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.