TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6866	20821;20822;20823	chr2:178725608;178725607;178725606	chr2:179590335;179590334;179590333
N2AB	6549	19870;19871;19872	chr2:178725608;178725607;178725606	chr2:179590335;179590334;179590333
N2A	5622	17089;17090;17091	chr2:178725608;178725607;178725606	chr2:179590335;179590334;179590333
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-53
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.2469
• 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/I	None	None	0.005	N	0.235	0.162	0.387042434762	gnomAD-4.0.0	1.60772E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88416E-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	0.1186	likely_benign	0.1146	benign	-0.76	Destabilizing	0.625	D	0.489	neutral	N	0.504427361	None	None	N
V/C	0.7004	likely_pathogenic	0.7156	pathogenic	-0.784	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	N
V/D	0.2852	likely_benign	0.3152	benign	-0.358	Destabilizing	0.974	D	0.53	neutral	None	None	None	None	N
V/E	0.2077	likely_benign	0.2129	benign	-0.44	Destabilizing	0.966	D	0.497	neutral	N	0.508563744	None	None	N
V/F	0.1109	likely_benign	0.112	benign	-0.733	Destabilizing	0.949	D	0.499	neutral	None	None	None	None	N
V/G	0.2055	likely_benign	0.204	benign	-0.941	Destabilizing	0.966	D	0.513	neutral	N	0.50518939	None	None	N
V/H	0.416	ambiguous	0.4216	ambiguous	-0.325	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
V/I	0.0722	likely_benign	0.0711	benign	-0.416	Destabilizing	0.005	N	0.235	neutral	N	0.454828047	None	None	N
V/K	0.2113	likely_benign	0.2169	benign	-0.659	Destabilizing	0.974	D	0.497	neutral	None	None	None	None	N
V/L	0.1154	likely_benign	0.1131	benign	-0.416	Destabilizing	0.267	N	0.32	neutral	N	0.459599149	None	None	N
V/M	0.1017	likely_benign	0.0996	benign	-0.465	Destabilizing	0.325	N	0.341	neutral	None	None	None	None	N
V/N	0.2232	likely_benign	0.2406	benign	-0.486	Destabilizing	0.974	D	0.543	neutral	None	None	None	None	N
V/P	0.3402	ambiguous	0.3557	ambiguous	-0.495	Destabilizing	0.991	D	0.521	neutral	None	None	None	None	N
V/Q	0.2171	likely_benign	0.2193	benign	-0.707	Destabilizing	0.974	D	0.529	neutral	None	None	None	None	N
V/R	0.1748	likely_benign	0.1871	benign	-0.09	Destabilizing	0.974	D	0.546	neutral	None	None	None	None	N
V/S	0.1676	likely_benign	0.1677	benign	-0.918	Destabilizing	0.728	D	0.486	neutral	None	None	None	None	N
V/T	0.1188	likely_benign	0.1154	benign	-0.896	Destabilizing	0.067	N	0.321	neutral	None	None	None	None	N
V/W	0.6281	likely_pathogenic	0.6444	pathogenic	-0.803	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
V/Y	0.4134	ambiguous	0.4148	ambiguous	-0.527	Destabilizing	0.991	D	0.515	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.