TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30666	92221;92222;92223	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
N2AB	29025	87298;87299;87300	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
N2A	28098	84517;84518;84519	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
N2B	21601	65026;65027;65028	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
Novex-1	21726	65401;65402;65403	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
Novex-2	21793	65602;65603;65604	chr2:178549726;178549725;178549724	chr2:179414453;179414452;179414451
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-111
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.5204
• 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
A/T	None	None	0.201	N	0.423	0.035	0.211220785272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/V	None	None	0.334	N	0.403	0.293	0.425028116352	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.5993	likely_pathogenic	0.6292	pathogenic	-0.65	Destabilizing	0.947	D	0.449	neutral	None	None	None	None	I
A/D	0.8147	likely_pathogenic	0.8698	pathogenic	-0.42	Destabilizing	0.468	N	0.551	neutral	N	0.488502611	None	None	I
A/E	0.7548	likely_pathogenic	0.8077	pathogenic	-0.521	Destabilizing	0.25	N	0.437	neutral	None	None	None	None	I
A/F	0.5903	likely_pathogenic	0.6619	pathogenic	-0.778	Destabilizing	0.826	D	0.638	neutral	None	None	None	None	I
A/G	0.2725	likely_benign	0.3143	benign	-0.531	Destabilizing	0.094	N	0.463	neutral	N	0.480229845	None	None	I
A/H	0.7411	likely_pathogenic	0.7827	pathogenic	-0.453	Destabilizing	0.947	D	0.633	neutral	None	None	None	None	I
A/I	0.4344	ambiguous	0.4993	ambiguous	-0.268	Destabilizing	0.7	D	0.501	neutral	None	None	None	None	I
A/K	0.8976	likely_pathogenic	0.9164	pathogenic	-0.704	Destabilizing	0.25	N	0.434	neutral	None	None	None	None	I
A/L	0.2672	likely_benign	0.3007	benign	-0.268	Destabilizing	0.399	N	0.453	neutral	None	None	None	None	I
A/M	0.3691	ambiguous	0.42	ambiguous	-0.448	Destabilizing	0.982	D	0.493	neutral	None	None	None	None	I
A/N	0.4213	ambiguous	0.4988	ambiguous	-0.376	Destabilizing	0.539	D	0.569	neutral	None	None	None	None	I
A/P	0.6855	likely_pathogenic	0.7412	pathogenic	-0.279	Destabilizing	0.638	D	0.505	neutral	N	0.499837113	None	None	I
A/Q	0.589	likely_pathogenic	0.6262	pathogenic	-0.586	Destabilizing	0.7	D	0.487	neutral	None	None	None	None	I
A/R	0.8333	likely_pathogenic	0.8472	pathogenic	-0.28	Destabilizing	0.7	D	0.499	neutral	None	None	None	None	I
A/S	0.1172	likely_benign	0.1315	benign	-0.631	Destabilizing	0.001	N	0.306	neutral	N	0.428992948	None	None	I
A/T	0.1367	likely_benign	0.155	benign	-0.644	Destabilizing	0.201	N	0.423	neutral	N	0.454064751	None	None	I
A/V	0.2141	likely_benign	0.256	benign	-0.279	Destabilizing	0.334	N	0.403	neutral	N	0.474152021	None	None	I
A/W	0.9199	likely_pathogenic	0.9358	pathogenic	-0.974	Destabilizing	0.982	D	0.737	prob.delet.	None	None	None	None	I
A/Y	0.7578	likely_pathogenic	0.8049	pathogenic	-0.607	Destabilizing	0.826	D	0.629	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.