TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21416	64471;64472;64473	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
N2AB	19775	59548;59549;59550	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
N2A	18848	56767;56768;56769	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
N2B	12351	37276;37277;37278	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
Novex-1	12476	37651;37652;37653	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
Novex-2	12543	37852;37853;37854	chr2:178586655;178586654;178586653	chr2:179451382;179451381;179451380
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-43
• Domain position: 51
• Structural Position: 66
• Q(SASA): 0.3011
• 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
T/I	None	None	1.0	N	0.717	0.375	0.370789594751	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43303E-05	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
T/A	0.1201	likely_benign	0.1158	benign	-0.892	Destabilizing	0.998	D	0.525	neutral	N	0.503549422	None	None	N
T/C	0.5281	ambiguous	0.5177	ambiguous	-0.536	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
T/D	0.5863	likely_pathogenic	0.5334	ambiguous	0.417	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
T/E	0.3576	ambiguous	0.3142	benign	0.439	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/F	0.3699	ambiguous	0.3497	ambiguous	-0.913	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/G	0.394	ambiguous	0.3883	ambiguous	-1.149	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
T/H	0.3162	likely_benign	0.3036	benign	-1.199	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/I	0.1876	likely_benign	0.1618	benign	-0.297	Destabilizing	1.0	D	0.717	prob.delet.	N	0.473362588	None	None	N
T/K	0.2507	likely_benign	0.2148	benign	-0.414	Destabilizing	0.999	D	0.68	prob.neutral	N	0.469108774	None	None	N
T/L	0.1292	likely_benign	0.1203	benign	-0.297	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
T/M	0.0962	likely_benign	0.0971	benign	-0.222	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
T/N	0.1618	likely_benign	0.1573	benign	-0.398	Destabilizing	0.91	D	0.274	neutral	None	None	None	None	N
T/P	0.6701	likely_pathogenic	0.6071	pathogenic	-0.464	Destabilizing	1.0	D	0.709	prob.delet.	N	0.488992514	None	None	N
T/Q	0.2336	likely_benign	0.2216	benign	-0.499	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/R	0.2426	likely_benign	0.2125	benign	-0.225	Destabilizing	0.999	D	0.722	prob.delet.	N	0.450928445	None	None	N
T/S	0.1561	likely_benign	0.1613	benign	-0.809	Destabilizing	0.996	D	0.5	neutral	N	0.461510798	None	None	N
T/V	0.1331	likely_benign	0.1238	benign	-0.464	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
T/W	0.6898	likely_pathogenic	0.6688	pathogenic	-0.801	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
T/Y	0.3953	ambiguous	0.3749	ambiguous	-0.566	Destabilizing	1.0	D	0.737	prob.delet.	None	None	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.