TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17056	51391;51392;51393	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
N2AB	15415	46468;46469;46470	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
N2A	14488	43687;43688;43689	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
N2B	7991	24196;24197;24198	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
Novex-1	8116	24571;24572;24573	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
Novex-2	8183	24772;24773;24774	chr2:178610360;178610359;178610358	chr2:179475087;179475086;179475085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-12
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3585
• 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
A/E	rs747241356	-0.784	0.999	D	0.79	0.406	0.619842255389	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
A/E	rs747241356	-0.784	0.999	D	0.79	0.406	0.619842255389	gnomAD-4.0.0	4.10808E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99941E-07	5.80019E-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
A/C	0.5612	ambiguous	0.599	pathogenic	-0.841	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
A/D	0.9091	likely_pathogenic	0.9044	pathogenic	-0.528	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
A/E	0.8554	likely_pathogenic	0.863	pathogenic	-0.583	Destabilizing	0.999	D	0.79	deleterious	D	0.536929611	None	None	N
A/F	0.6772	likely_pathogenic	0.6906	pathogenic	-0.747	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/G	0.261	likely_benign	0.2851	benign	-0.756	Destabilizing	0.996	D	0.607	neutral	D	0.601950174	None	None	N
A/H	0.8893	likely_pathogenic	0.891	pathogenic	-0.799	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
A/I	0.3633	ambiguous	0.3777	ambiguous	-0.155	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
A/K	0.9525	likely_pathogenic	0.9559	pathogenic	-0.92	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
A/L	0.4178	ambiguous	0.4278	ambiguous	-0.155	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
A/M	0.4835	ambiguous	0.4941	ambiguous	-0.317	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/N	0.7505	likely_pathogenic	0.7623	pathogenic	-0.665	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
A/P	0.1895	likely_benign	0.2414	benign	-0.245	Destabilizing	0.999	D	0.839	deleterious	N	0.49077398	None	None	N
A/Q	0.8423	likely_pathogenic	0.8503	pathogenic	-0.794	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/R	0.9396	likely_pathogenic	0.9398	pathogenic	-0.588	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/S	0.1873	likely_benign	0.199	benign	-1.002	Destabilizing	0.957	D	0.385	neutral	N	0.484594738	None	None	N
A/T	0.1934	likely_benign	0.2045	benign	-0.946	Destabilizing	0.992	D	0.673	neutral	N	0.518984083	None	None	N
A/V	0.1791	likely_benign	0.183	benign	-0.245	Destabilizing	0.998	D	0.678	prob.neutral	N	0.422091778	None	None	N
A/W	0.9464	likely_pathogenic	0.9524	pathogenic	-1.027	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/Y	0.7938	likely_pathogenic	0.8072	pathogenic	-0.621	Destabilizing	1.0	D	0.863	deleterious	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.