TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15246	45961;45962;45963	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
N2AB	13605	41038;41039;41040	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
N2A	12678	38257;38258;38259	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
N2B	6181	18766;18767;18768	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
Novex-1	6306	19141;19142;19143	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
Novex-2	6373	19342;19343;19344	chr2:178620874;178620873;178620872	chr2:179485601;179485600;179485599
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-104
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.4172
• 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
A/G	None	None	0.309	N	0.301	0.252	0.385743280973	gnomAD-4.0.0	6.84668E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.999E-07	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	0.6938	likely_pathogenic	0.7033	pathogenic	-0.561	Destabilizing	0.996	D	0.389	neutral	None	None	None	None	N
A/D	0.3321	likely_benign	0.3294	benign	-0.235	Destabilizing	0.684	D	0.392	neutral	N	0.491397408	None	None	N
A/E	0.246	likely_benign	0.2468	benign	-0.292	Destabilizing	0.742	D	0.371	neutral	None	None	None	None	N
A/F	0.4793	ambiguous	0.4994	ambiguous	-0.632	Destabilizing	0.953	D	0.455	neutral	None	None	None	None	N
A/G	0.1949	likely_benign	0.1919	benign	-0.589	Destabilizing	0.309	N	0.301	neutral	N	0.513364596	None	None	N
A/H	0.6097	likely_pathogenic	0.6174	pathogenic	-0.52	Destabilizing	0.996	D	0.431	neutral	None	None	None	None	N
A/I	0.2338	likely_benign	0.2898	benign	-0.106	Destabilizing	0.742	D	0.384	neutral	None	None	None	None	N
A/K	0.5107	ambiguous	0.4897	ambiguous	-0.623	Destabilizing	0.742	D	0.361	neutral	None	None	None	None	N
A/L	0.1907	likely_benign	0.218	benign	-0.106	Destabilizing	0.373	N	0.37	neutral	None	None	None	None	N
A/M	0.229	likely_benign	0.2645	benign	-0.318	Destabilizing	0.984	D	0.387	neutral	None	None	None	None	N
A/N	0.2315	likely_benign	0.2463	benign	-0.394	Destabilizing	0.742	D	0.427	neutral	None	None	None	None	N
A/P	0.1226	likely_benign	0.1335	benign	-0.17	Destabilizing	0.007	N	0.197	neutral	N	0.435421429	None	None	N
A/Q	0.3784	ambiguous	0.3723	ambiguous	-0.526	Destabilizing	0.91	D	0.4	neutral	None	None	None	None	N
A/R	0.5056	ambiguous	0.4719	ambiguous	-0.299	Destabilizing	0.91	D	0.403	neutral	None	None	None	None	N
A/S	0.1097	likely_benign	0.1145	benign	-0.714	Destabilizing	0.012	N	0.167	neutral	N	0.492365868	None	None	N
A/T	0.0866	likely_benign	0.0993	benign	-0.67	Destabilizing	0.004	N	0.127	neutral	N	0.410493262	None	None	N
A/V	0.1227	likely_benign	0.1447	benign	-0.17	Destabilizing	0.309	N	0.319	neutral	N	0.484837139	None	None	N
A/W	0.8419	likely_pathogenic	0.824	pathogenic	-0.907	Destabilizing	0.996	D	0.485	neutral	None	None	None	None	N
A/Y	0.6154	likely_pathogenic	0.6192	pathogenic	-0.492	Destabilizing	0.984	D	0.455	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.