TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6684	20275;20276;20277	chr2:178727315;178727314;178727313	chr2:179592042;179592041;179592040
N2AB	6367	19324;19325;19326	chr2:178727315;178727314;178727313	chr2:179592042;179592041;179592040
N2A	5440	16543;16544;16545	chr2:178727315;178727314;178727313	chr2:179592042;179592041;179592040
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-51
• Domain position: 18
• Structural Position: 26
• Q(SASA): 0.3738
• 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
S/Y	None	None	0.999	N	0.706	0.376	0.503186968135	gnomAD-4.0.0	1.59571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86589E-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
S/A	0.0772	likely_benign	0.0735	benign	-0.507	Destabilizing	0.948	D	0.405	neutral	N	0.457061694	None	None	N
S/C	0.1777	likely_benign	0.1727	benign	-0.246	Destabilizing	1.0	D	0.631	neutral	N	0.501374506	None	None	N
S/D	0.3549	ambiguous	0.3475	ambiguous	-0.205	Destabilizing	0.992	D	0.482	neutral	None	None	None	None	N
S/E	0.5063	ambiguous	0.5036	ambiguous	-0.277	Destabilizing	0.992	D	0.471	neutral	None	None	None	None	N
S/F	0.1296	likely_benign	0.1189	benign	-1.03	Destabilizing	0.999	D	0.705	prob.neutral	N	0.501121017	None	None	N
S/G	0.1135	likely_benign	0.1142	benign	-0.66	Destabilizing	0.992	D	0.402	neutral	None	None	None	None	N
S/H	0.3203	likely_benign	0.3209	benign	-1.243	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
S/I	0.1597	likely_benign	0.1508	benign	-0.223	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
S/K	0.6539	likely_pathogenic	0.6697	pathogenic	-0.52	Destabilizing	0.992	D	0.485	neutral	None	None	None	None	N
S/L	0.1035	likely_benign	0.0996	benign	-0.223	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
S/M	0.214	likely_benign	0.2102	benign	0.25	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
S/N	0.1462	likely_benign	0.1451	benign	-0.315	Destabilizing	0.997	D	0.503	neutral	None	None	None	None	N
S/P	0.1727	likely_benign	0.1688	benign	-0.287	Destabilizing	0.121	N	0.272	neutral	N	0.455540757	None	None	N
S/Q	0.4748	ambiguous	0.4823	ambiguous	-0.619	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
S/R	0.5505	ambiguous	0.5762	pathogenic	-0.29	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
S/T	0.0865	likely_benign	0.0831	benign	-0.391	Destabilizing	0.989	D	0.395	neutral	N	0.470233777	None	None	N
S/V	0.1583	likely_benign	0.1536	benign	-0.287	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	N
S/W	0.3156	likely_benign	0.3139	benign	-1.002	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
S/Y	0.1432	likely_benign	0.1366	benign	-0.727	Destabilizing	0.999	D	0.706	prob.neutral	N	0.478408406	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.