TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9494	28705;28706;28707	chr2:178709839;178709838;178709837	chr2:179574566;179574565;179574564
N2AB	9177	27754;27755;27756	chr2:178709839;178709838;178709837	chr2:179574566;179574565;179574564
N2A	8250	24973;24974;24975	chr2:178709839;178709838;178709837	chr2:179574566;179574565;179574564
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-81
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1399
• 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/C	rs1553886767	None	0.978	None	0.512	0.446	0.437207349437	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/N	None	None	0.002	None	0.23	0.136	0.193865811164	gnomAD-4.0.0	1.59582E-06	None	None	None	None	N	None	0	0	None	0	2.77454E-05	None	0	0	0	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
S/A	0.0853	likely_benign	0.0908	benign	-0.36	Destabilizing	0.129	N	0.321	neutral	None	None	None	None	N
S/C	0.1358	likely_benign	0.182	benign	-0.382	Destabilizing	0.978	D	0.512	neutral	None	None	None	None	N
S/D	0.604	likely_pathogenic	0.7306	pathogenic	0.509	Stabilizing	0.002	N	0.213	neutral	None	None	None	None	N
S/E	0.6199	likely_pathogenic	0.7439	pathogenic	0.454	Stabilizing	0.129	N	0.415	neutral	None	None	None	None	N
S/F	0.2134	likely_benign	0.2593	benign	-0.962	Destabilizing	0.716	D	0.534	neutral	None	None	None	None	N
S/G	0.1292	likely_benign	0.1526	benign	-0.487	Destabilizing	0.101	N	0.403	neutral	None	None	None	None	N
S/H	0.3665	ambiguous	0.5211	ambiguous	-0.792	Destabilizing	0.716	D	0.529	neutral	None	None	None	None	N
S/I	0.14	likely_benign	0.1827	benign	-0.15	Destabilizing	0.213	N	0.525	neutral	None	None	None	None	N
S/K	0.7014	likely_pathogenic	0.8295	pathogenic	-0.207	Destabilizing	0.264	N	0.441	neutral	None	None	None	None	N
S/L	0.1048	likely_benign	0.1363	benign	-0.15	Destabilizing	0.129	N	0.489	neutral	None	None	None	None	N
S/M	0.1931	likely_benign	0.2511	benign	-0.217	Destabilizing	0.061	N	0.435	neutral	None	None	None	None	N
S/N	0.1554	likely_benign	0.23	benign	-0.11	Destabilizing	0.002	N	0.23	neutral	None	None	None	None	N
S/P	0.882	likely_pathogenic	0.9468	pathogenic	-0.191	Destabilizing	0.593	D	0.565	neutral	None	None	None	None	N
S/Q	0.4885	ambiguous	0.6433	pathogenic	-0.221	Destabilizing	0.716	D	0.542	neutral	None	None	None	None	N
S/R	0.5966	likely_pathogenic	0.7419	pathogenic	-0.069	Destabilizing	0.655	D	0.564	neutral	None	None	None	None	N
S/T	0.0678	likely_benign	0.0723	benign	-0.197	Destabilizing	0.007	N	0.211	neutral	None	None	None	None	N
S/V	0.1357	likely_benign	0.1636	benign	-0.191	Destabilizing	0.01	N	0.439	neutral	None	None	None	None	N
S/W	0.5193	ambiguous	0.6359	pathogenic	-1.013	Destabilizing	0.983	D	0.58	neutral	None	None	None	None	N
S/Y	0.2318	likely_benign	0.3003	benign	-0.678	Destabilizing	0.94	D	0.557	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.