TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8049	24370;24371;24372	chr2:178719245;178719244;178719243	chr2:179583972;179583971;179583970
N2AB	7732	23419;23420;23421	chr2:178719245;178719244;178719243	chr2:179583972;179583971;179583970
N2A	6805	20638;20639;20640	chr2:178719245;178719244;178719243	chr2:179583972;179583971;179583970
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-65
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.4853
• 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
P/L	None	None	0.001	N	0.214	0.184	0.278968121808	gnomAD-4.0.0	1.59127E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43283E-05	0
P/S	None	None	None	N	0.16	0.136	0.0611884634855	gnomAD-4.0.0	1.59126E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85838E-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
P/A	0.0711	likely_benign	0.0651	benign	-0.59	Destabilizing	0.019	N	0.239	neutral	N	0.460440858	None	None	I
P/C	0.3647	ambiguous	0.3561	ambiguous	-0.657	Destabilizing	0.883	D	0.331	neutral	None	None	None	None	I
P/D	0.1894	likely_benign	0.1874	benign	-0.36	Destabilizing	0.22	N	0.267	neutral	None	None	None	None	I
P/E	0.1485	likely_benign	0.1422	benign	-0.471	Destabilizing	0.124	N	0.269	neutral	None	None	None	None	I
P/F	0.2363	likely_benign	0.2338	benign	-0.8	Destabilizing	0.497	N	0.357	neutral	None	None	None	None	I
P/G	0.1662	likely_benign	0.1559	benign	-0.739	Destabilizing	0.055	N	0.294	neutral	None	None	None	None	I
P/H	0.1148	likely_benign	0.1068	benign	-0.282	Destabilizing	0.602	D	0.325	neutral	N	0.513717982	None	None	I
P/I	0.1646	likely_benign	0.1623	benign	-0.345	Destabilizing	0.124	N	0.321	neutral	None	None	None	None	I
P/K	0.1344	likely_benign	0.1365	benign	-0.47	Destabilizing	0.004	N	0.215	neutral	None	None	None	None	I
P/L	0.0849	likely_benign	0.0809	benign	-0.345	Destabilizing	0.001	N	0.214	neutral	N	0.430579311	None	None	I
P/M	0.1784	likely_benign	0.1811	benign	-0.331	Destabilizing	0.497	N	0.337	neutral	None	None	None	None	I
P/N	0.1457	likely_benign	0.1455	benign	-0.193	Destabilizing	0.124	N	0.37	neutral	None	None	None	None	I
P/Q	0.1037	likely_benign	0.0949	benign	-0.456	Destabilizing	0.22	N	0.377	neutral	None	None	None	None	I
P/R	0.1069	likely_benign	0.1004	benign	0.081	Stabilizing	0.003	N	0.194	neutral	N	0.423114621	None	None	I
P/S	0.082	likely_benign	0.0755	benign	-0.583	Destabilizing	None	N	0.16	neutral	N	0.444164683	None	None	I
P/T	0.0793	likely_benign	0.0729	benign	-0.59	Destabilizing	0.042	N	0.263	neutral	N	0.45897942	None	None	I
P/V	0.1276	likely_benign	0.1261	benign	-0.391	Destabilizing	None	N	0.143	neutral	None	None	None	None	I
P/W	0.3543	ambiguous	0.3471	ambiguous	-0.862	Destabilizing	0.958	D	0.373	neutral	None	None	None	None	I
P/Y	0.2074	likely_benign	0.201	benign	-0.561	Destabilizing	0.667	D	0.356	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.