TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6223	18892;18893;18894	chr2:178729489;178729488;178729487	chr2:179594216;179594215;179594214
N2AB	5906	17941;17942;17943	chr2:178729489;178729488;178729487	chr2:179594216;179594215;179594214
N2A	4979	15160;15161;15162	chr2:178729489;178729488;178729487	chr2:179594216;179594215;179594214
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: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-46
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4211
• 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/M	rs794727817	-0.231	0.004	D	0.18	0.111	0.437634105008	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.9E-06	0
T/M	rs794727817	-0.231	0.004	D	0.18	0.111	0.437634105008	gnomAD-4.0.0	1.50547E-05	None	None	None	None	N	None	0	0	None	0	2.52042E-05	None	0	0	1.70918E-05	2.31889E-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	0.0663	likely_benign	0.0697	benign	-0.712	Destabilizing	None	N	0.063	neutral	N	0.463236886	None	None	N
T/C	0.3291	likely_benign	0.3967	ambiguous	-0.439	Destabilizing	0.356	N	0.277	neutral	None	None	None	None	N
T/D	0.2751	likely_benign	0.3102	benign	0.432	Stabilizing	0.038	N	0.275	neutral	None	None	None	None	N
T/E	0.1798	likely_benign	0.2026	benign	0.431	Stabilizing	0.016	N	0.294	neutral	None	None	None	None	N
T/F	0.1416	likely_benign	0.165	benign	-0.867	Destabilizing	None	N	0.218	neutral	None	None	None	None	N
T/G	0.1726	likely_benign	0.2123	benign	-0.948	Destabilizing	0.016	N	0.257	neutral	None	None	None	None	N
T/H	0.1566	likely_benign	0.1868	benign	-1.134	Destabilizing	0.356	N	0.312	neutral	None	None	None	None	N
T/I	0.1127	likely_benign	0.127	benign	-0.183	Destabilizing	0.038	N	0.277	neutral	None	None	None	None	N
T/K	0.111	likely_benign	0.1194	benign	-0.411	Destabilizing	None	N	0.147	neutral	N	0.480763855	None	None	N
T/L	0.0748	likely_benign	0.0809	benign	-0.183	Destabilizing	0.006	N	0.291	neutral	None	None	None	None	N
T/M	0.0727	likely_benign	0.0744	benign	-0.085	Destabilizing	0.004	N	0.18	neutral	D	0.525229495	None	None	N
T/N	0.1047	likely_benign	0.1148	benign	-0.362	Destabilizing	0.001	N	0.181	neutral	None	None	None	None	N
T/P	0.4478	ambiguous	0.458	ambiguous	-0.327	Destabilizing	0.055	N	0.332	neutral	N	0.508978506	None	None	N
T/Q	0.133	likely_benign	0.1519	benign	-0.467	Destabilizing	0.072	N	0.332	neutral	None	None	None	None	N
T/R	0.0818	likely_benign	0.0839	benign	-0.247	Destabilizing	0.07	N	0.271	neutral	N	0.489538053	None	None	N
T/S	0.0796	likely_benign	0.0919	benign	-0.713	Destabilizing	None	N	0.099	neutral	N	0.4428989	None	None	N
T/V	0.1076	likely_benign	0.1183	benign	-0.327	Destabilizing	0.016	N	0.219	neutral	None	None	None	None	N
T/W	0.3418	ambiguous	0.3908	ambiguous	-0.805	Destabilizing	0.864	D	0.312	neutral	None	None	None	None	N
T/Y	0.1879	likely_benign	0.2189	benign	-0.546	Destabilizing	0.12	N	0.397	neutral	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.