TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6110	18553;18554;18555	chr2:178729925;178729924;178729923	chr2:179594652;179594651;179594650
N2AB	5793	17602;17603;17604	chr2:178729925;178729924;178729923	chr2:179594652;179594651;179594650
N2A	4866	14821;14822;14823	chr2:178729925;178729924;178729923	chr2:179594652;179594651;179594650
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-45
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.4776
• 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
K/N	rs1350814757	None	0.891	N	0.44	0.261	0.173771789658	gnomAD-4.0.0	1.5942E-06	None	None	None	None	N	None	0	2.29632E-05	None	0	0	None	0	0	0	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
K/A	0.4499	ambiguous	0.4081	ambiguous	-0.324	Destabilizing	0.688	D	0.46	neutral	None	None	None	None	N
K/C	0.8264	likely_pathogenic	0.7924	pathogenic	-0.354	Destabilizing	0.998	D	0.549	neutral	None	None	None	None	N
K/D	0.7152	likely_pathogenic	0.65	pathogenic	0.349	Stabilizing	0.915	D	0.503	neutral	None	None	None	None	N
K/E	0.2247	likely_benign	0.1928	benign	0.429	Stabilizing	0.891	D	0.457	neutral	N	0.489166254	None	None	N
K/F	0.7633	likely_pathogenic	0.7124	pathogenic	-0.195	Destabilizing	0.949	D	0.561	neutral	None	None	None	None	N
K/G	0.6154	likely_pathogenic	0.5453	ambiguous	-0.627	Destabilizing	0.915	D	0.532	neutral	None	None	None	None	N
K/H	0.4317	ambiguous	0.3949	ambiguous	-0.9	Destabilizing	0.998	D	0.5	neutral	None	None	None	None	N
K/I	0.3505	ambiguous	0.3115	benign	0.429	Stabilizing	0.728	D	0.542	neutral	None	None	None	None	N
K/L	0.35	ambiguous	0.3171	benign	0.429	Stabilizing	0.275	N	0.485	neutral	None	None	None	None	N
K/M	0.1836	likely_benign	0.1696	benign	0.152	Stabilizing	0.267	N	0.359	neutral	N	0.485775012	None	None	N
K/N	0.4774	ambiguous	0.4125	ambiguous	0.002	Stabilizing	0.891	D	0.44	neutral	N	0.473009447	None	None	N
K/P	0.6124	likely_pathogenic	0.5909	pathogenic	0.208	Stabilizing	0.991	D	0.506	neutral	None	None	None	None	N
K/Q	0.1513	likely_benign	0.1379	benign	-0.056	Destabilizing	0.966	D	0.484	neutral	N	0.493169352	None	None	N
K/R	0.1099	likely_benign	0.105	benign	-0.251	Destabilizing	0.891	D	0.443	neutral	N	0.487704817	None	None	N
K/S	0.5155	ambiguous	0.4518	ambiguous	-0.629	Destabilizing	0.525	D	0.425	neutral	None	None	None	None	N
K/T	0.2118	likely_benign	0.1882	benign	-0.354	Destabilizing	0.022	N	0.245	neutral	N	0.48428051	None	None	N
K/V	0.3713	ambiguous	0.3318	benign	0.208	Stabilizing	0.728	D	0.528	neutral	None	None	None	None	N
K/W	0.8174	likely_pathogenic	0.7729	pathogenic	-0.121	Destabilizing	0.998	D	0.576	neutral	None	None	None	None	N
K/Y	0.6178	likely_pathogenic	0.5505	ambiguous	0.187	Stabilizing	0.974	D	0.565	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.