TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3981	12166;12167;12168	chr2:178741292;178741291;178741290	chr2:179606019;179606018;179606017
N2AB	3664	11215;11216;11217	chr2:178741292;178741291;178741290	chr2:179606019;179606018;179606017
N2A	None	None	chr2:None	chr2:None
N2B	3618	11077;11078;11079	chr2:178741292;178741291;178741290	chr2:179606019;179606018;179606017
Novex-1	3743	11452;11453;11454	chr2:178741292;178741291;178741290	chr2:179606019;179606018;179606017
Novex-2	3810	11653;11654;11655	chr2:178741292;178741291;178741290	chr2:179606019;179606018;179606017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-28
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2021
• 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
S/T	rs761366397	0.017	0.027	N	0.373	0.102	0.0401082797425	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/T	rs761366397	0.017	0.027	N	0.373	0.102	0.0401082797425	gnomAD-4.0.0	3.18219E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85789E-06	1.43271E-05	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
S/A	0.2049	likely_benign	0.1666	benign	-0.605	Destabilizing	0.035	N	0.374	neutral	None	None	None	None	N
S/C	0.191	likely_benign	0.1645	benign	-0.379	Destabilizing	0.915	D	0.303	neutral	N	0.520776159	None	None	N
S/D	0.2884	likely_benign	0.216	benign	0.674	Stabilizing	0.001	N	0.154	neutral	None	None	None	None	N
S/E	0.7106	likely_pathogenic	0.6068	pathogenic	0.641	Stabilizing	0.035	N	0.335	neutral	None	None	None	None	N
S/F	0.6882	likely_pathogenic	0.5924	pathogenic	-1.077	Destabilizing	0.791	D	0.347	neutral	None	None	None	None	N
S/G	0.096	likely_benign	0.085	benign	-0.775	Destabilizing	None	N	0.135	neutral	N	0.445407988	None	None	N
S/H	0.4519	ambiguous	0.3721	ambiguous	-1.107	Destabilizing	0.38	N	0.283	neutral	None	None	None	None	N
S/I	0.518	ambiguous	0.4261	ambiguous	-0.273	Destabilizing	0.484	N	0.359	neutral	D	0.601657669	None	None	N
S/K	0.8073	likely_pathogenic	0.7221	pathogenic	-0.237	Destabilizing	0.081	N	0.329	neutral	None	None	None	None	N
S/L	0.3524	ambiguous	0.2954	benign	-0.273	Destabilizing	0.149	N	0.376	neutral	None	None	None	None	N
S/M	0.476	ambiguous	0.3977	ambiguous	-0.207	Destabilizing	0.935	D	0.277	neutral	None	None	None	None	N
S/N	0.0811	likely_benign	0.0751	benign	-0.155	Destabilizing	None	N	0.122	neutral	N	0.452847835	None	None	N
S/P	0.7976	likely_pathogenic	0.7345	pathogenic	-0.353	Destabilizing	0.555	D	0.323	neutral	None	None	None	None	N
S/Q	0.7304	likely_pathogenic	0.6403	pathogenic	-0.246	Destabilizing	0.38	N	0.339	neutral	None	None	None	None	N
S/R	0.7342	likely_pathogenic	0.6401	pathogenic	-0.164	Destabilizing	0.317	N	0.349	neutral	D	0.523610775	None	None	N
S/T	0.124	likely_benign	0.1103	benign	-0.28	Destabilizing	0.027	N	0.373	neutral	N	0.456526959	None	None	N
S/V	0.5337	ambiguous	0.4413	ambiguous	-0.353	Destabilizing	0.262	N	0.392	neutral	None	None	None	None	N
S/W	0.762	likely_pathogenic	0.6879	pathogenic	-1.065	Destabilizing	0.935	D	0.497	neutral	None	None	None	None	N
S/Y	0.4898	ambiguous	0.4177	ambiguous	-0.767	Destabilizing	0.791	D	0.343	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.