TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7773	23542;23543;23544	chr2:178720445;178720444;178720443	chr2:179585172;179585171;179585170
N2AB	7456	22591;22592;22593	chr2:178720445;178720444;178720443	chr2:179585172;179585171;179585170
N2A	6529	19810;19811;19812	chr2:178720445;178720444;178720443	chr2:179585172;179585171;179585170
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-62
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.3992
• 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
H/Y	rs777185633	0.873	None	N	0.216	0.048	0.141422826196	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	0	0
H/Y	rs777185633	0.873	None	N	0.216	0.048	0.141422826196	gnomAD-4.0.0	5.47414E-06	None	None	None	None	N	None	0	8.94494E-05	None	0	0	None	0	0	1.79908E-06	0	3.31356E-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
H/A	0.2214	likely_benign	0.2337	benign	-0.689	Destabilizing	0.004	N	0.452	neutral	None	None	None	None	N
H/C	0.156	likely_benign	0.1772	benign	0.054	Stabilizing	0.497	N	0.524	neutral	None	None	None	None	N
H/D	0.2561	likely_benign	0.2957	benign	-0.457	Destabilizing	0.003	N	0.367	neutral	N	0.459190064	None	None	N
H/E	0.2393	likely_benign	0.2662	benign	-0.367	Destabilizing	None	N	0.193	neutral	None	None	None	None	N
H/F	0.1869	likely_benign	0.2007	benign	0.315	Stabilizing	0.022	N	0.509	neutral	None	None	None	None	N
H/G	0.3595	ambiguous	0.3921	ambiguous	-1.049	Destabilizing	0.008	N	0.431	neutral	None	None	None	None	N
H/I	0.1301	likely_benign	0.1408	benign	0.297	Stabilizing	0.044	N	0.531	neutral	None	None	None	None	N
H/K	0.2785	likely_benign	0.296	benign	-0.487	Destabilizing	0.004	N	0.362	neutral	None	None	None	None	N
H/L	0.0862	likely_benign	0.0894	benign	0.297	Stabilizing	0.007	N	0.437	neutral	N	0.38902069	None	None	N
H/M	0.3176	likely_benign	0.3309	benign	0.175	Stabilizing	0.245	N	0.537	neutral	None	None	None	None	N
H/N	0.0917	likely_benign	0.1002	benign	-0.474	Destabilizing	0.014	N	0.395	neutral	N	0.440430945	None	None	N
H/P	0.847	likely_pathogenic	0.8563	pathogenic	-0.011	Destabilizing	0.065	N	0.543	neutral	N	0.496361585	None	None	N
H/Q	0.1152	likely_benign	0.1251	benign	-0.243	Destabilizing	None	N	0.186	neutral	N	0.332898048	None	None	N
H/R	0.1244	likely_benign	0.129	benign	-0.927	Destabilizing	0.007	N	0.382	neutral	N	0.369472137	None	None	N
H/S	0.151	likely_benign	0.1645	benign	-0.543	Destabilizing	0.001	N	0.267	neutral	None	None	None	None	N
H/T	0.1464	likely_benign	0.1582	benign	-0.352	Destabilizing	0.009	N	0.449	neutral	None	None	None	None	N
H/V	0.1244	likely_benign	0.1291	benign	-0.011	Destabilizing	0.018	N	0.465	neutral	None	None	None	None	N
H/W	0.357	ambiguous	0.3698	ambiguous	0.51	Stabilizing	0.245	N	0.534	neutral	None	None	None	None	N
H/Y	0.077	likely_benign	0.0837	benign	0.708	Stabilizing	None	N	0.216	neutral	N	0.43094467	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.