TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27031	81316;81317;81318	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
N2AB	25390	76393;76394;76395	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
N2A	24463	73612;73613;73614	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
N2B	17966	54121;54122;54123	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
Novex-1	18091	54496;54497;54498	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
Novex-2	18158	54697;54698;54699	chr2:178565041;178565040;178565039	chr2:179429768;179429767;179429766
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-84
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2312
• 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
T/A	None	None	0.63	N	0.448	0.237	0.24896430686	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87287E-05	0	8.99536E-07	0	0
T/I	rs777849777	0.398	0.983	N	0.641	0.437	0.513394077459	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/I	rs777849777	0.398	0.983	N	0.641	0.437	0.513394077459	gnomAD-4.0.0	5.47434E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19635E-06	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
T/A	0.0918	likely_benign	0.0862	benign	-0.888	Destabilizing	0.63	D	0.448	neutral	N	0.472155706	None	None	N
T/C	0.4656	ambiguous	0.4532	ambiguous	-0.497	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/D	0.6795	likely_pathogenic	0.6644	pathogenic	-0.457	Destabilizing	0.975	D	0.622	neutral	None	None	None	None	N
T/E	0.5685	likely_pathogenic	0.5492	ambiguous	-0.33	Destabilizing	0.845	D	0.56	neutral	None	None	None	None	N
T/F	0.4104	ambiguous	0.3695	ambiguous	-0.678	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
T/G	0.3101	likely_benign	0.2738	benign	-1.258	Destabilizing	0.845	D	0.569	neutral	None	None	None	None	N
T/H	0.3858	ambiguous	0.3606	ambiguous	-1.418	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
T/I	0.3108	likely_benign	0.3028	benign	0.051	Stabilizing	0.983	D	0.641	neutral	N	0.483222524	None	None	N
T/K	0.3836	ambiguous	0.3715	ambiguous	-0.443	Destabilizing	0.056	N	0.427	neutral	N	0.516846793	None	None	N
T/L	0.1645	likely_benign	0.1526	benign	0.051	Stabilizing	0.916	D	0.539	neutral	None	None	None	None	N
T/M	0.1051	likely_benign	0.0975	benign	0.047	Stabilizing	0.999	D	0.669	neutral	None	None	None	None	N
T/N	0.1686	likely_benign	0.1602	benign	-0.802	Destabilizing	0.975	D	0.562	neutral	None	None	None	None	N
T/P	0.8181	likely_pathogenic	0.8221	pathogenic	-0.229	Destabilizing	0.983	D	0.639	neutral	N	0.494489923	None	None	N
T/Q	0.3112	likely_benign	0.2902	benign	-0.692	Destabilizing	0.975	D	0.641	neutral	None	None	None	None	N
T/R	0.3239	likely_benign	0.3215	benign	-0.517	Destabilizing	0.935	D	0.613	neutral	N	0.496951523	None	None	N
T/S	0.1172	likely_benign	0.1064	benign	-1.098	Destabilizing	0.099	N	0.495	neutral	N	0.435534918	None	None	N
T/V	0.183	likely_benign	0.1812	benign	-0.229	Destabilizing	0.916	D	0.505	neutral	None	None	None	None	N
T/W	0.821	likely_pathogenic	0.7885	pathogenic	-0.742	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
T/Y	0.4719	ambiguous	0.4401	ambiguous	-0.404	Destabilizing	0.996	D	0.73	prob.delet.	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.