TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21105	63538;63539;63540	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
N2AB	19464	58615;58616;58617	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
N2A	18537	55834;55835;55836	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
N2B	12040	36343;36344;36345	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
Novex-1	12165	36718;36719;36720	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
Novex-2	12232	36919;36920;36921	chr2:178588094;178588093;178588092	chr2:179452821;179452820;179452819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-41
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2061
• 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
P/L	rs773378006	-0.522	0.003	N	0.371	0.161	0.370608029945	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
P/L	rs773378006	-0.522	0.003	N	0.371	0.161	0.370608029945	gnomAD-4.0.0	4.77937E-06	None	None	None	None	N	None	0	0	None	0	5.56917E-05	None	1.88288E-05	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
P/A	0.1047	likely_benign	0.1073	benign	-1.547	Destabilizing	0.684	D	0.417	neutral	N	0.472421225	None	None	N
P/C	0.49	ambiguous	0.4995	ambiguous	-0.838	Destabilizing	0.996	D	0.672	neutral	None	None	None	None	N
P/D	0.4268	ambiguous	0.4414	ambiguous	-1.508	Destabilizing	0.009	N	0.339	neutral	None	None	None	None	N
P/E	0.2059	likely_benign	0.2031	benign	-1.475	Destabilizing	0.59	D	0.415	neutral	None	None	None	None	N
P/F	0.6017	likely_pathogenic	0.5882	pathogenic	-1.087	Destabilizing	0.91	D	0.673	neutral	None	None	None	None	N
P/G	0.2761	likely_benign	0.2875	benign	-1.892	Destabilizing	0.742	D	0.529	neutral	None	None	None	None	N
P/H	0.2228	likely_benign	0.2207	benign	-1.457	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
P/I	0.3658	ambiguous	0.3716	ambiguous	-0.678	Destabilizing	0.59	D	0.553	neutral	None	None	None	None	N
P/K	0.1873	likely_benign	0.1818	benign	-1.334	Destabilizing	0.742	D	0.483	neutral	None	None	None	None	N
P/L	0.1373	likely_benign	0.1406	benign	-0.678	Destabilizing	0.003	N	0.371	neutral	N	0.443485185	None	None	N
P/M	0.3283	likely_benign	0.3321	benign	-0.451	Destabilizing	0.91	D	0.623	neutral	None	None	None	None	N
P/N	0.3273	likely_benign	0.3271	benign	-1.14	Destabilizing	0.91	D	0.583	neutral	None	None	None	None	N
P/Q	0.1186	likely_benign	0.1174	benign	-1.272	Destabilizing	0.939	D	0.559	neutral	N	0.461510798	None	None	N
P/R	0.1482	likely_benign	0.1463	benign	-0.817	Destabilizing	0.939	D	0.624	neutral	N	0.464052458	None	None	N
P/S	0.148	likely_benign	0.1502	benign	-1.644	Destabilizing	0.684	D	0.453	neutral	N	0.45835585	None	None	N
P/T	0.1435	likely_benign	0.1502	benign	-1.507	Destabilizing	0.684	D	0.459	neutral	N	0.446312059	None	None	N
P/V	0.2334	likely_benign	0.2397	benign	-0.934	Destabilizing	0.59	D	0.494	neutral	None	None	None	None	N
P/W	0.6175	likely_pathogenic	0.6288	pathogenic	-1.356	Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
P/Y	0.4952	ambiguous	0.496	ambiguous	-1.056	Destabilizing	0.953	D	0.673	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.