TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7736	23431;23432;23433	chr2:178720556;178720555;178720554	chr2:179585283;179585282;179585281
N2AB	7419	22480;22481;22482	chr2:178720556;178720555;178720554	chr2:179585283;179585282;179585281
N2A	6492	19699;19700;19701	chr2:178720556;178720555;178720554	chr2:179585283;179585282;179585281
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-62
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1834
• 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
V/D	None	None	0.351	N	0.593	0.248	0.611053723974	gnomAD-4.0.0	1.59208E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85961E-06	0	0
V/F	rs770301886	-1.303	None	N	0.214	0.287	0.395745362164	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	5.81E-05	None	0	0	None	0	None	0	8.91E-06	0
V/F	rs770301886	-1.303	None	N	0.214	0.287	0.395745362164	gnomAD-4.0.0	7.96062E-06	None	None	None	None	N	None	0	4.57477E-05	None	0	0	None	0	0	8.57913E-06	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
V/A	0.2516	likely_benign	0.2702	benign	-1.827	Destabilizing	0.183	N	0.332	neutral	N	0.399200398	None	None	N
V/C	0.7109	likely_pathogenic	0.7065	pathogenic	-1.171	Destabilizing	0.94	D	0.538	neutral	None	None	None	None	N
V/D	0.4842	ambiguous	0.5397	ambiguous	-2.446	Highly Destabilizing	0.351	N	0.593	neutral	N	0.463019803	None	None	N
V/E	0.3284	likely_benign	0.3758	ambiguous	-2.314	Highly Destabilizing	0.129	N	0.511	neutral	None	None	None	None	N
V/F	0.082	likely_benign	0.0714	benign	-1.191	Destabilizing	None	N	0.214	neutral	N	0.315907011	None	None	N
V/G	0.2543	likely_benign	0.2774	benign	-2.278	Highly Destabilizing	0.523	D	0.565	neutral	N	0.481605564	None	None	N
V/H	0.4956	ambiguous	0.5209	ambiguous	-2.158	Highly Destabilizing	0.002	N	0.438	neutral	None	None	None	None	N
V/I	0.0799	likely_benign	0.0774	benign	-0.608	Destabilizing	0.001	N	0.175	neutral	N	0.414841854	None	None	N
V/K	0.5317	ambiguous	0.5853	pathogenic	-1.652	Destabilizing	0.264	N	0.559	neutral	None	None	None	None	N
V/L	0.1403	likely_benign	0.1439	benign	-0.608	Destabilizing	0.017	N	0.311	neutral	N	0.355926836	None	None	N
V/M	0.1003	likely_benign	0.0975	benign	-0.419	Destabilizing	0.716	D	0.52	neutral	None	None	None	None	N
V/N	0.2925	likely_benign	0.3128	benign	-1.721	Destabilizing	0.418	N	0.618	neutral	None	None	None	None	N
V/P	0.9826	likely_pathogenic	0.9849	pathogenic	-0.985	Destabilizing	0.94	D	0.635	neutral	None	None	None	None	N
V/Q	0.3092	likely_benign	0.3359	benign	-1.691	Destabilizing	0.027	N	0.401	neutral	None	None	None	None	N
V/R	0.4627	ambiguous	0.5131	ambiguous	-1.331	Destabilizing	0.418	N	0.626	neutral	None	None	None	None	N
V/S	0.2228	likely_benign	0.2398	benign	-2.23	Highly Destabilizing	0.418	N	0.529	neutral	None	None	None	None	N
V/T	0.2111	likely_benign	0.2245	benign	-1.983	Destabilizing	0.228	N	0.391	neutral	None	None	None	None	N
V/W	0.6383	likely_pathogenic	0.6116	pathogenic	-1.736	Destabilizing	0.94	D	0.603	neutral	None	None	None	None	N
V/Y	0.3243	likely_benign	0.3078	benign	-1.353	Destabilizing	0.004	N	0.207	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.