TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8509	25750;25751;25752	chr2:178717209;178717208;178717207	chr2:179581936;179581935;179581934
N2AB	8192	24799;24800;24801	chr2:178717209;178717208;178717207	chr2:179581936;179581935;179581934
N2A	7265	22018;22019;22020	chr2:178717209;178717208;178717207	chr2:179581936;179581935;179581934
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-70
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4141
• 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
N/D	None	None	0.198	N	0.325	0.243	0.253726318573	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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
N/A	0.5769	likely_pathogenic	0.6049	pathogenic	-0.625	Destabilizing	0.986	D	0.681	prob.neutral	None	None	None	None	N
N/C	0.7494	likely_pathogenic	0.794	pathogenic	0.248	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
N/D	0.2001	likely_benign	0.2068	benign	-0.376	Destabilizing	0.198	N	0.325	neutral	N	0.511662765	None	None	N
N/E	0.6104	likely_pathogenic	0.6272	pathogenic	-0.303	Destabilizing	0.994	D	0.551	neutral	None	None	None	None	N
N/F	0.8785	likely_pathogenic	0.8969	pathogenic	-0.454	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
N/G	0.4175	ambiguous	0.4268	ambiguous	-0.953	Destabilizing	0.999	D	0.516	neutral	None	None	None	None	N
N/H	0.2219	likely_benign	0.2344	benign	-0.904	Destabilizing	1.0	D	0.676	prob.neutral	D	0.524182699	None	None	N
N/I	0.787	likely_pathogenic	0.8169	pathogenic	0.196	Stabilizing	1.0	D	0.755	deleterious	N	0.513079883	None	None	N
N/K	0.4971	ambiguous	0.5259	ambiguous	-0.283	Destabilizing	0.999	D	0.625	neutral	N	0.48889556	None	None	N
N/L	0.7264	likely_pathogenic	0.7625	pathogenic	0.196	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
N/M	0.694	likely_pathogenic	0.7275	pathogenic	0.619	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
N/P	0.9412	likely_pathogenic	0.9455	pathogenic	-0.047	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
N/Q	0.5249	ambiguous	0.5483	ambiguous	-0.723	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/R	0.6004	likely_pathogenic	0.6307	pathogenic	-0.408	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
N/S	0.1905	likely_benign	0.1954	benign	-0.704	Destabilizing	0.988	D	0.521	neutral	D	0.533115472	None	None	N
N/T	0.3944	ambiguous	0.4142	ambiguous	-0.451	Destabilizing	0.996	D	0.612	neutral	N	0.48918873	None	None	N
N/V	0.7777	likely_pathogenic	0.8088	pathogenic	-0.047	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
N/W	0.9384	likely_pathogenic	0.9492	pathogenic	-0.31	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
N/Y	0.3311	likely_benign	0.3678	ambiguous	-0.094	Destabilizing	1.0	D	0.728	prob.delet.	N	0.519409759	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.