TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26615	80068;80069;80070	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
N2AB	24974	75145;75146;75147	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
N2A	24047	72364;72365;72366	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
N2B	17550	52873;52874;52875	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
Novex-1	17675	53248;53249;53250	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
Novex-2	17742	53449;53450;53451	chr2:178566289;178566288;178566287	chr2:179431016;179431015;179431014
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: Ig-138
• Domain position: 22
• Structural Position: 34
• Q(SASA): 0.3338
• 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/A	None	None	0.958	D	0.613	0.414	0.386721274199	gnomAD-4.0.0	6.8426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99526E-07	0	0
P/S	None	None	0.994	N	0.774	0.323	0.398581233421	gnomAD-4.0.0	1.36852E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7343E-04	0	0	1.65695E-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
P/A	0.1491	likely_benign	0.1564	benign	-1.185	Destabilizing	0.958	D	0.613	neutral	D	0.530016452	None	None	N
P/C	0.661	likely_pathogenic	0.6671	pathogenic	-0.672	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/D	0.8525	likely_pathogenic	0.837	pathogenic	-1.294	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
P/E	0.7171	likely_pathogenic	0.712	pathogenic	-1.28	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
P/F	0.7179	likely_pathogenic	0.7253	pathogenic	-0.89	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
P/G	0.5289	ambiguous	0.5645	pathogenic	-1.481	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
P/H	0.4363	ambiguous	0.4362	ambiguous	-0.983	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
P/I	0.4552	ambiguous	0.4607	ambiguous	-0.472	Destabilizing	0.334	N	0.591	neutral	None	None	None	None	N
P/K	0.6471	likely_pathogenic	0.6424	pathogenic	-1.081	Destabilizing	0.995	D	0.795	deleterious	None	None	None	None	N
P/L	0.1849	likely_benign	0.2005	benign	-0.472	Destabilizing	0.797	D	0.703	prob.neutral	N	0.502062291	None	None	N
P/M	0.512	ambiguous	0.5314	ambiguous	-0.392	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
P/N	0.6272	likely_pathogenic	0.6257	pathogenic	-0.958	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
P/Q	0.4001	ambiguous	0.4088	ambiguous	-1.099	Destabilizing	0.998	D	0.806	deleterious	N	0.493602367	None	None	N
P/R	0.4461	ambiguous	0.4404	ambiguous	-0.559	Destabilizing	0.998	D	0.792	deleterious	D	0.532806041	None	None	N
P/S	0.2785	likely_benign	0.2801	benign	-1.365	Destabilizing	0.994	D	0.774	deleterious	N	0.516375151	None	None	N
P/T	0.219	likely_benign	0.2217	benign	-1.246	Destabilizing	0.988	D	0.739	prob.delet.	N	0.487975042	None	None	N
P/V	0.3461	ambiguous	0.3529	ambiguous	-0.676	Destabilizing	0.839	D	0.633	neutral	None	None	None	None	N
P/W	0.8565	likely_pathogenic	0.8736	pathogenic	-1.135	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/Y	0.6878	likely_pathogenic	0.7033	pathogenic	-0.806	Destabilizing	0.999	D	0.784	deleterious	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.