TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19119	57580;57581;57582	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
N2AB	17478	52657;52658;52659	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
N2A	16551	49876;49877;49878	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
N2B	10054	30385;30386;30387	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
Novex-1	10179	30760;30761;30762	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
Novex-2	10246	30961;30962;30963	chr2:178597727;178597726;178597725	chr2:179462454;179462453;179462452
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-117
• Domain position: 25
• Structural Position: 41
• Q(SASA): 0.6739
• Predicted PPI site: I

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/M	rs1576219870	None	1.0	D	0.728	0.489	0.488548280593	gnomAD-4.0.0	1.59232E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-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
K/A	0.8623	likely_pathogenic	0.9167	pathogenic	0.064	Stabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
K/C	0.8937	likely_pathogenic	0.9104	pathogenic	-0.377	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
K/D	0.9739	likely_pathogenic	0.9865	pathogenic	-0.258	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/E	0.7416	likely_pathogenic	0.8708	pathogenic	-0.258	Destabilizing	0.999	D	0.709	prob.delet.	N	0.459599149	None	None	I
K/F	0.9288	likely_pathogenic	0.9511	pathogenic	-0.218	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
K/G	0.9439	likely_pathogenic	0.9672	pathogenic	-0.091	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
K/H	0.5607	ambiguous	0.6389	pathogenic	-0.211	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
K/I	0.654	likely_pathogenic	0.7133	pathogenic	0.391	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
K/L	0.7251	likely_pathogenic	0.7971	pathogenic	0.391	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
K/M	0.5471	ambiguous	0.622	pathogenic	-0.041	Destabilizing	1.0	D	0.728	prob.delet.	D	0.531616749	None	None	I
K/N	0.8828	likely_pathogenic	0.9331	pathogenic	0.048	Stabilizing	1.0	D	0.778	deleterious	N	0.4699895	None	None	I
K/P	0.9928	likely_pathogenic	0.9947	pathogenic	0.307	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/Q	0.3177	likely_benign	0.4481	ambiguous	-0.075	Destabilizing	1.0	D	0.773	deleterious	N	0.463332887	None	None	I
K/R	0.1081	likely_benign	0.1268	benign	-0.075	Destabilizing	0.999	D	0.649	neutral	N	0.421120905	None	None	I
K/S	0.8736	likely_pathogenic	0.9324	pathogenic	-0.304	Destabilizing	0.999	D	0.738	prob.delet.	None	None	None	None	I
K/T	0.6442	likely_pathogenic	0.7579	pathogenic	-0.178	Destabilizing	1.0	D	0.719	prob.delet.	N	0.478531626	None	None	I
K/V	0.6481	likely_pathogenic	0.7091	pathogenic	0.307	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
K/W	0.9336	likely_pathogenic	0.9548	pathogenic	-0.327	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
K/Y	0.8234	likely_pathogenic	0.879	pathogenic	0.029	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I

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.