TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3900	11923;11924;11925	chr2:178741535;178741534;178741533	chr2:179606262;179606261;179606260
N2AB	3583	10972;10973;10974	chr2:178741535;178741534;178741533	chr2:179606262;179606261;179606260
N2A	None	None	chr2:None	chr2:None
N2B	3537	10834;10835;10836	chr2:178741535;178741534;178741533	chr2:179606262;179606261;179606260
Novex-1	3662	11209;11210;11211	chr2:178741535;178741534;178741533	chr2:179606262;179606261;179606260
Novex-2	3729	11410;11411;11412	chr2:178741535;178741534;178741533	chr2:179606262;179606261;179606260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-27
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6097
• 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
K/N	None	None	0.055	N	0.335	0.192	None	gnomAD-4.0.0	1.59119E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85802E-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
K/A	0.333	likely_benign	0.2772	benign	-0.216	Destabilizing	0.016	N	0.439	neutral	None	None	None	None	I
K/C	0.645	likely_pathogenic	0.6246	pathogenic	-0.273	Destabilizing	0.864	D	0.485	neutral	None	None	None	None	I
K/D	0.4248	ambiguous	0.3738	ambiguous	0.102	Stabilizing	0.016	N	0.471	neutral	None	None	None	None	I
K/E	0.0943	likely_benign	0.0814	benign	0.136	Stabilizing	None	N	0.137	neutral	N	0.417185629	None	None	I
K/F	0.7071	likely_pathogenic	0.6442	pathogenic	-0.262	Destabilizing	0.628	D	0.487	neutral	None	None	None	None	I
K/G	0.4145	ambiguous	0.3638	ambiguous	-0.471	Destabilizing	0.072	N	0.497	neutral	None	None	None	None	I
K/H	0.3031	likely_benign	0.2659	benign	-0.771	Destabilizing	0.214	N	0.471	neutral	None	None	None	None	I
K/I	0.2872	likely_benign	0.2414	benign	0.395	Stabilizing	0.356	N	0.491	neutral	None	None	None	None	I
K/L	0.3304	likely_benign	0.2782	benign	0.395	Stabilizing	0.072	N	0.498	neutral	None	None	None	None	I
K/M	0.1739	likely_benign	0.1452	benign	0.241	Stabilizing	0.295	N	0.481	neutral	N	0.520520526	None	None	I
K/N	0.2388	likely_benign	0.1978	benign	0.072	Stabilizing	0.055	N	0.335	neutral	N	0.510430258	None	None	I
K/P	0.8373	likely_pathogenic	0.7873	pathogenic	0.221	Stabilizing	0.136	N	0.497	neutral	None	None	None	None	I
K/Q	0.101	likely_benign	0.0901	benign	-0.091	Destabilizing	None	N	0.136	neutral	N	0.474133832	None	None	I
K/R	0.0886	likely_benign	0.0832	benign	-0.188	Destabilizing	None	N	0.135	neutral	N	0.504987924	None	None	I
K/S	0.2981	likely_benign	0.2482	benign	-0.499	Destabilizing	0.016	N	0.382	neutral	None	None	None	None	I
K/T	0.1368	likely_benign	0.1108	benign	-0.294	Destabilizing	0.055	N	0.449	neutral	N	0.471048417	None	None	I
K/V	0.2859	likely_benign	0.2413	benign	0.221	Stabilizing	0.072	N	0.512	neutral	None	None	None	None	I
K/W	0.7296	likely_pathogenic	0.6815	pathogenic	-0.203	Destabilizing	0.864	D	0.491	neutral	None	None	None	None	I
K/Y	0.5249	ambiguous	0.4771	ambiguous	0.117	Stabilizing	0.356	N	0.486	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.