TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8577	25954;25955;25956	chr2:178715685;178715684;178715683	chr2:179580412;179580411;179580410
N2AB	8260	25003;25004;25005	chr2:178715685;178715684;178715683	chr2:179580412;179580411;179580410
N2A	7333	22222;22223;22224	chr2:178715685;178715684;178715683	chr2:179580412;179580411;179580410
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-71
• Domain position: 29
• Structural Position: 42
• Q(SASA): 0.4941
• Predicted PPI site: I

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/T	None	None	0.03	D	0.261	0.602	0.418095516054	gnomAD-4.0.0	1.59731E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86814E-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
P/A	0.2924	likely_benign	0.3013	benign	-0.343	Destabilizing	0.02	N	0.269	neutral	D	0.558164207	None	None	I
P/C	0.913	likely_pathogenic	0.9203	pathogenic	-0.579	Destabilizing	0.994	D	0.648	neutral	None	None	None	None	I
P/D	0.8251	likely_pathogenic	0.8399	pathogenic	-0.328	Destabilizing	0.776	D	0.457	neutral	None	None	None	None	I
P/E	0.6203	likely_pathogenic	0.6269	pathogenic	-0.461	Destabilizing	0.846	D	0.465	neutral	None	None	None	None	I
P/F	0.9192	likely_pathogenic	0.9156	pathogenic	-0.73	Destabilizing	0.994	D	0.654	neutral	None	None	None	None	I
P/G	0.6864	likely_pathogenic	0.707	pathogenic	-0.433	Destabilizing	0.713	D	0.519	neutral	None	None	None	None	I
P/H	0.6194	likely_pathogenic	0.6263	pathogenic	-0.111	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I
P/I	0.7778	likely_pathogenic	0.76	pathogenic	-0.265	Destabilizing	0.977	D	0.613	neutral	None	None	None	None	I
P/K	0.6829	likely_pathogenic	0.6717	pathogenic	-0.346	Destabilizing	0.989	D	0.465	neutral	None	None	None	None	I
P/L	0.4043	ambiguous	0.3555	ambiguous	-0.265	Destabilizing	0.903	D	0.554	neutral	D	0.622922335	None	None	I
P/M	0.7202	likely_pathogenic	0.6963	pathogenic	-0.321	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	I
P/N	0.7878	likely_pathogenic	0.7926	pathogenic	-0.068	Destabilizing	0.956	D	0.556	neutral	None	None	None	None	I
P/Q	0.4739	ambiguous	0.4721	ambiguous	-0.334	Destabilizing	0.993	D	0.453	neutral	D	0.52524738	None	None	I
P/R	0.5089	ambiguous	0.5014	ambiguous	0.152	Stabilizing	0.992	D	0.564	neutral	D	0.631805312	None	None	I
P/S	0.4456	ambiguous	0.4688	ambiguous	-0.371	Destabilizing	0.721	D	0.437	neutral	D	0.562430168	None	None	I
P/T	0.3484	ambiguous	0.3348	benign	-0.41	Destabilizing	0.03	N	0.261	neutral	D	0.622518726	None	None	I
P/V	0.6019	likely_pathogenic	0.5904	pathogenic	-0.258	Destabilizing	0.118	N	0.264	neutral	None	None	None	None	I
P/W	0.9331	likely_pathogenic	0.9339	pathogenic	-0.808	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/Y	0.905	likely_pathogenic	0.9031	pathogenic	-0.498	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	I

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.