TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1620	5083;5084;5085	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
N2AB	1620	5083;5084;5085	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
N2A	1620	5083;5084;5085	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
N2B	1574	4945;4946;4947	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
Novex-1	1574	4945;4946;4947	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
Novex-2	1574	4945;4946;4947	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731
Novex-3	1620	5083;5084;5085	chr2:178777006;178777005;178777004	chr2:179641733;179641732;179641731

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-7
• Domain position: 65
• Structural Position: 144
• Q(SASA): 0.0939
• 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/A	None	None	0.001	N	0.222	0.104	0.159798565429	gnomAD-4.0.0	1.59077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85665E-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
T/A	0.0837	likely_benign	0.0786	benign	-1.076	Destabilizing	0.001	N	0.222	neutral	N	0.44698644	None	None	N
T/C	0.4904	ambiguous	0.4576	ambiguous	-1.394	Destabilizing	0.935	D	0.605	neutral	None	None	None	None	N
T/D	0.9017	likely_pathogenic	0.8992	pathogenic	-1.858	Destabilizing	0.38	N	0.626	neutral	None	None	None	None	N
T/E	0.8529	likely_pathogenic	0.8481	pathogenic	-1.771	Destabilizing	0.149	N	0.611	neutral	None	None	None	None	N
T/F	0.6587	likely_pathogenic	0.6451	pathogenic	-1.332	Destabilizing	0.38	N	0.621	neutral	None	None	None	None	N
T/G	0.497	ambiguous	0.4874	ambiguous	-1.325	Destabilizing	0.149	N	0.552	neutral	None	None	None	None	N
T/H	0.8237	likely_pathogenic	0.8225	pathogenic	-1.537	Destabilizing	0.935	D	0.601	neutral	None	None	None	None	N
T/I	0.1108	likely_benign	0.1115	benign	-0.477	Destabilizing	0.001	N	0.416	neutral	N	0.496907105	None	None	N
T/K	0.8298	likely_pathogenic	0.8214	pathogenic	-0.758	Destabilizing	0.149	N	0.609	neutral	None	None	None	None	N
T/L	0.1269	likely_benign	0.1164	benign	-0.477	Destabilizing	0.012	N	0.521	neutral	None	None	None	None	N
T/M	0.1298	likely_benign	0.129	benign	-0.389	Destabilizing	0.38	N	0.618	neutral	None	None	None	None	N
T/N	0.4878	ambiguous	0.4729	ambiguous	-1.237	Destabilizing	0.317	N	0.601	neutral	D	0.589367013	None	None	N
T/P	0.253	likely_benign	0.2557	benign	-0.649	Destabilizing	0.484	N	0.631	neutral	N	0.511580302	None	None	N
T/Q	0.786	likely_pathogenic	0.7861	pathogenic	-1.413	Destabilizing	0.555	D	0.651	neutral	None	None	None	None	N
T/R	0.7508	likely_pathogenic	0.7438	pathogenic	-0.558	Destabilizing	0.555	D	0.627	neutral	None	None	None	None	N
T/S	0.2274	likely_benign	0.218	benign	-1.366	Destabilizing	0.005	N	0.351	neutral	N	0.509838353	None	None	N
T/V	0.0974	likely_benign	0.0925	benign	-0.649	Destabilizing	0.012	N	0.509	neutral	None	None	None	None	N
T/W	0.9575	likely_pathogenic	0.9549	pathogenic	-1.368	Destabilizing	0.935	D	0.612	neutral	None	None	None	None	N
T/Y	0.8582	likely_pathogenic	0.8541	pathogenic	-0.983	Destabilizing	0.555	D	0.617	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.