TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19469	58630;58631;58632	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
N2AB	17828	53707;53708;53709	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
N2A	16901	50926;50927;50928	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
N2B	10404	31435;31436;31437	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
Novex-1	10529	31810;31811;31812	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
Novex-2	10596	32011;32012;32013	chr2:178593988;178593987;178593986	chr2:179458715;179458714;179458713
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-118
• Domain position: 79
• Structural Position: 168
• Q(SASA): 0.3285
• 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
K/R	rs551642842	-0.011	0.99	N	0.459	0.264	0.505701759113	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs551642842	-0.011	0.99	N	0.459	0.264	0.505701759113	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None

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
K/A	0.5465	ambiguous	0.5504	ambiguous	-0.44	Destabilizing	0.931	D	0.447	neutral	None	None	None	None	N
K/C	0.818	likely_pathogenic	0.8202	pathogenic	-0.564	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/D	0.7505	likely_pathogenic	0.7751	pathogenic	0.201	Stabilizing	0.996	D	0.546	neutral	None	None	None	None	N
K/E	0.2323	likely_benign	0.2288	benign	0.309	Stabilizing	0.98	D	0.415	neutral	N	0.470352073	None	None	N
K/F	0.8872	likely_pathogenic	0.8852	pathogenic	-0.243	Destabilizing	0.996	D	0.69	prob.neutral	None	None	None	None	N
K/G	0.7444	likely_pathogenic	0.749	pathogenic	-0.757	Destabilizing	0.985	D	0.574	neutral	None	None	None	None	N
K/H	0.4378	ambiguous	0.4459	ambiguous	-0.873	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
K/I	0.5006	ambiguous	0.507	ambiguous	0.362	Stabilizing	0.989	D	0.604	neutral	D	0.522266547	None	None	N
K/L	0.5437	ambiguous	0.542	ambiguous	0.362	Stabilizing	0.171	N	0.419	neutral	None	None	None	None	N
K/M	0.3266	likely_benign	0.3198	benign	-0.02	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
K/N	0.6017	likely_pathogenic	0.615	pathogenic	-0.296	Destabilizing	0.994	D	0.439	neutral	N	0.517532731	None	None	N
K/P	0.9468	likely_pathogenic	0.9489	pathogenic	0.124	Stabilizing	0.998	D	0.593	neutral	None	None	None	None	N
K/Q	0.1758	likely_benign	0.1707	benign	-0.289	Destabilizing	0.997	D	0.517	neutral	N	0.507142379	None	None	N
K/R	0.0956	likely_benign	0.0939	benign	-0.277	Destabilizing	0.99	D	0.459	neutral	N	0.490596846	None	None	N
K/S	0.532	ambiguous	0.537	ambiguous	-0.911	Destabilizing	0.719	D	0.311	neutral	None	None	None	None	N
K/T	0.2056	likely_benign	0.2072	benign	-0.603	Destabilizing	0.4	N	0.32	neutral	N	0.443493546	None	None	N
K/V	0.4412	ambiguous	0.4489	ambiguous	0.124	Stabilizing	0.971	D	0.543	neutral	None	None	None	None	N
K/W	0.8621	likely_pathogenic	0.8478	pathogenic	-0.187	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/Y	0.7542	likely_pathogenic	0.7514	pathogenic	0.114	Stabilizing	0.999	D	0.667	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.