TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22048	66367;66368;66369	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
N2AB	20407	61444;61445;61446	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
N2A	19480	58663;58664;58665	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
N2B	12983	39172;39173;39174	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
Novex-1	13108	39547;39548;39549	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
Novex-2	13175	39748;39749;39750	chr2:178582314;178582313;178582312	chr2:179447041;179447040;179447039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-47
• Domain position: 93
• Structural Position: 128
• Q(SASA): 0.3228
• 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
I/M	rs980906933	None	0.001	N	0.217	0.073	0.192905019026	gnomAD-4.0.0	6.66274E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.49128E-04	8.84215E-06	0	0
I/N	None	None	0.162	N	0.541	0.174	0.690481662768	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
I/V	rs1282316821	None	None	N	0.1	0.061	0.194818534648	gnomAD-4.0.0	1.66088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94291E-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
I/A	0.2174	likely_benign	0.1684	benign	-1.08	Destabilizing	0.007	N	0.438	neutral	None	None	None	None	N
I/C	0.6699	likely_pathogenic	0.5895	pathogenic	-0.63	Destabilizing	0.492	N	0.355	neutral	None	None	None	None	N
I/D	0.7944	likely_pathogenic	0.6994	pathogenic	-0.683	Destabilizing	0.068	N	0.547	neutral	None	None	None	None	N
I/E	0.5383	ambiguous	0.4432	ambiguous	-0.756	Destabilizing	0.035	N	0.479	neutral	None	None	None	None	N
I/F	0.1698	likely_benign	0.1461	benign	-0.914	Destabilizing	0.087	N	0.389	neutral	N	0.478776568	None	None	N
I/G	0.6778	likely_pathogenic	0.5822	pathogenic	-1.306	Destabilizing	0.068	N	0.487	neutral	None	None	None	None	N
I/H	0.5281	ambiguous	0.4501	ambiguous	-0.536	Destabilizing	0.747	D	0.421	neutral	None	None	None	None	N
I/K	0.304	likely_benign	0.2504	benign	-0.706	Destabilizing	None	N	0.425	neutral	None	None	None	None	N
I/L	0.1107	likely_benign	0.0978	benign	-0.583	Destabilizing	0.002	N	0.239	neutral	N	0.493802149	None	None	N
I/M	0.1041	likely_benign	0.0944	benign	-0.432	Destabilizing	0.001	N	0.217	neutral	N	0.475008531	None	None	N
I/N	0.401	ambiguous	0.3188	benign	-0.438	Destabilizing	0.162	N	0.541	neutral	N	0.479790526	None	None	N
I/P	0.6335	likely_pathogenic	0.5089	ambiguous	-0.715	Destabilizing	0.204	N	0.529	neutral	None	None	None	None	N
I/Q	0.3801	ambiguous	0.3067	benign	-0.698	Destabilizing	0.112	N	0.533	neutral	None	None	None	None	N
I/R	0.2605	likely_benign	0.2081	benign	-0.048	Destabilizing	0.018	N	0.549	neutral	None	None	None	None	N
I/S	0.3148	likely_benign	0.2404	benign	-0.915	Destabilizing	0.013	N	0.392	neutral	N	0.4780161	None	None	N
I/T	0.106	likely_benign	0.0874	benign	-0.882	Destabilizing	None	N	0.375	neutral	N	0.477255631	None	None	N
I/V	0.0551	likely_benign	0.0536	benign	-0.715	Destabilizing	None	N	0.1	neutral	N	0.458844213	None	None	N
I/W	0.785	likely_pathogenic	0.7204	pathogenic	-0.931	Destabilizing	0.747	D	0.527	neutral	None	None	None	None	N
I/Y	0.5502	ambiguous	0.4596	ambiguous	-0.709	Destabilizing	0.204	N	0.484	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.