TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1618	5077;5078;5079	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
N2AB	1618	5077;5078;5079	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
N2A	1618	5077;5078;5079	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
N2B	1572	4939;4940;4941	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
Novex-1	1572	4939;4940;4941	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
Novex-2	1572	4939;4940;4941	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737
Novex-3	1618	5077;5078;5079	chr2:178777012;178777011;178777010	chr2:179641739;179641738;179641737

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-7
• Domain position: 63
• Structural Position: 141
• Q(SASA): 0.4402
• 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
D/G	rs1324756385	None	0.521	N	0.341	0.288	0.259761712551	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/G	rs1324756385	None	0.521	N	0.341	0.288	0.259761712551	gnomAD-4.0.0	2.02977E-06	None	None	None	None	N	None	3.49394E-05	0	None	0	0	None	0	0	0	0	0
D/H	None	None	0.975	N	0.401	0.209	0.3085936734	gnomAD-4.0.0	6.84134E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99313E-07	0	0
D/N	rs794727465	-0.135	0.037	N	0.18	0.118	0.184867976434	gnomAD-2.1.1	7.12E-06	None	None	None	None	N	None	4.12E-05	0	None	0	0	None	0	None	0	7.79E-06	0
D/N	rs794727465	-0.135	0.037	N	0.18	0.118	0.184867976434	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/N	rs794727465	-0.135	0.037	N	0.18	0.118	0.184867976434	gnomAD-4.0.0	4.33748E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93222E-06	0	0
D/Y	rs794727465	None	0.992	N	0.455	0.333	0.673333262281	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/Y	rs794727465	None	0.992	N	0.455	0.333	0.673333262281	gnomAD-4.0.0	1.23928E-06	None	None	None	None	N	None	1.33522E-05	0	None	0	0	None	0	0	0	0	1.60061E-05

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
D/A	0.1941	likely_benign	0.1763	benign	-0.306	Destabilizing	0.472	N	0.357	neutral	N	0.491652713	None	None	N
D/C	0.7478	likely_pathogenic	0.6954	pathogenic	0.032	Stabilizing	0.996	D	0.457	neutral	None	None	None	None	N
D/E	0.1501	likely_benign	0.1428	benign	-0.334	Destabilizing	0.003	N	0.075	neutral	N	0.453490999	None	None	N
D/F	0.5872	likely_pathogenic	0.55	ambiguous	-0.157	Destabilizing	0.984	D	0.455	neutral	None	None	None	None	N
D/G	0.2255	likely_benign	0.2031	benign	-0.53	Destabilizing	0.521	D	0.341	neutral	N	0.512818854	None	None	N
D/H	0.3641	ambiguous	0.3063	benign	-0.123	Destabilizing	0.975	D	0.401	neutral	N	0.503061684	None	None	N
D/I	0.3799	ambiguous	0.3338	benign	0.242	Stabilizing	0.91	D	0.47	neutral	None	None	None	None	N
D/K	0.5359	ambiguous	0.4481	ambiguous	0.328	Stabilizing	0.59	D	0.343	neutral	None	None	None	None	N
D/L	0.4	ambiguous	0.3619	ambiguous	0.242	Stabilizing	0.742	D	0.437	neutral	None	None	None	None	N
D/M	0.6467	likely_pathogenic	0.5983	pathogenic	0.414	Stabilizing	0.996	D	0.432	neutral	None	None	None	None	N
D/N	0.1271	likely_benign	0.1168	benign	-0.048	Destabilizing	0.037	N	0.18	neutral	N	0.459105581	None	None	N
D/P	0.5412	ambiguous	0.4861	ambiguous	0.083	Stabilizing	0.004	N	0.095	neutral	None	None	None	None	N
D/Q	0.4081	ambiguous	0.3553	ambiguous	-0.006	Destabilizing	0.59	D	0.346	neutral	None	None	None	None	N
D/R	0.5525	ambiguous	0.4723	ambiguous	0.457	Stabilizing	0.91	D	0.436	neutral	None	None	None	None	N
D/S	0.1393	likely_benign	0.1285	benign	-0.158	Destabilizing	0.373	N	0.291	neutral	None	None	None	None	N
D/T	0.2662	likely_benign	0.2361	benign	0.022	Stabilizing	0.037	N	0.198	neutral	None	None	None	None	N
D/V	0.2508	likely_benign	0.2217	benign	0.083	Stabilizing	0.684	D	0.439	neutral	N	0.511476828	None	None	N
D/W	0.9098	likely_pathogenic	0.8828	pathogenic	0.007	Stabilizing	0.996	D	0.535	neutral	None	None	None	None	N
D/Y	0.3129	likely_benign	0.2701	benign	0.094	Stabilizing	0.992	D	0.455	neutral	N	0.50945732	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.