TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5734	17425;17426;17427	chr2:178731566;178731565;178731564	chr2:179596293;179596292;179596291
N2AB	5417	16474;16475;16476	chr2:178731566;178731565;178731564	chr2:179596293;179596292;179596291
N2A	4490	13693;13694;13695	chr2:178731566;178731565;178731564	chr2:179596293;179596292;179596291
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-41
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6894
• 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/E	None	None	0.811	N	0.569	0.197	0.360961692134	gnomAD-4.0.0	1.61419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0641E-05

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	0.4728	ambiguous	0.4285	ambiguous	-0.138	Destabilizing	0.919	D	0.545	neutral	None	None	None	None	N
K/C	0.788	likely_pathogenic	0.749	pathogenic	-0.338	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/D	0.664	likely_pathogenic	0.6031	pathogenic	0.168	Stabilizing	0.976	D	0.52	neutral	None	None	None	None	N
K/E	0.1857	likely_benign	0.1662	benign	0.225	Stabilizing	0.811	D	0.569	neutral	N	0.492519643	None	None	N
K/F	0.8834	likely_pathogenic	0.8649	pathogenic	-0.037	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	N
K/G	0.4839	ambiguous	0.4428	ambiguous	-0.424	Destabilizing	0.959	D	0.476	neutral	None	None	None	None	N
K/H	0.3325	likely_benign	0.3183	benign	-0.65	Destabilizing	0.997	D	0.599	neutral	None	None	None	None	N
K/I	0.6225	likely_pathogenic	0.5731	pathogenic	0.56	Stabilizing	0.988	D	0.616	neutral	None	None	None	None	N
K/L	0.5224	ambiguous	0.4843	ambiguous	0.56	Stabilizing	0.919	D	0.476	neutral	None	None	None	None	N
K/M	0.3882	ambiguous	0.3555	ambiguous	0.261	Stabilizing	0.999	D	0.603	neutral	N	0.504610413	None	None	N
K/N	0.4937	ambiguous	0.4439	ambiguous	-0.016	Destabilizing	0.968	D	0.507	neutral	D	0.526517574	None	None	N
K/P	0.9189	likely_pathogenic	0.892	pathogenic	0.358	Stabilizing	0.996	D	0.594	neutral	None	None	None	None	N
K/Q	0.1098	likely_benign	0.1084	benign	-0.127	Destabilizing	0.251	N	0.197	neutral	N	0.444570981	None	None	N
K/R	0.0815	likely_benign	0.0833	benign	-0.231	Destabilizing	0.026	N	0.238	neutral	N	0.478878343	None	None	N
K/S	0.4391	ambiguous	0.4031	ambiguous	-0.59	Destabilizing	0.919	D	0.518	neutral	None	None	None	None	N
K/T	0.2423	likely_benign	0.2146	benign	-0.355	Destabilizing	0.984	D	0.532	neutral	N	0.509065177	None	None	N
K/V	0.5455	ambiguous	0.5005	ambiguous	0.358	Stabilizing	0.988	D	0.52	neutral	None	None	None	None	N
K/W	0.8046	likely_pathogenic	0.7933	pathogenic	0.018	Stabilizing	0.999	D	0.666	neutral	None	None	None	None	N
K/Y	0.7493	likely_pathogenic	0.7211	pathogenic	0.328	Stabilizing	0.996	D	0.603	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.