TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7769	23530;23531;23532	chr2:178720457;178720456;178720455	chr2:179585184;179585183;179585182
N2AB	7452	22579;22580;22581	chr2:178720457;178720456;178720455	chr2:179585184;179585183;179585182
N2A	6525	19798;19799;19800	chr2:178720457;178720456;178720455	chr2:179585184;179585183;179585182
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: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-62
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2535
• 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/A	None	None	0.027	N	0.433	0.101	0.332902724076	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79909E-06	0	0
V/F	None	None	0.188	N	0.587	0.154	0.279776271856	gnomAD-4.0.0	6.84269E-07	None	None	None	None	N	None	0	0	None	0	2.51953E-05	None	0	0	0	0	0
V/I	rs1553907172	None	None	N	0.129	0.122	0.101711395817	gnomAD-4.0.0	2.05281E-06	None	None	None	None	N	None	5.97836E-05	0	None	0	0	None	0	0	0	0	1.65684E-05

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	0.0947	likely_benign	0.1008	benign	-1.222	Destabilizing	0.027	N	0.433	neutral	N	0.387370904	None	None	N
V/C	0.5896	likely_pathogenic	0.6365	pathogenic	-0.967	Destabilizing	0.824	D	0.529	neutral	None	None	None	None	N
V/D	0.4044	ambiguous	0.4935	ambiguous	-0.212	Destabilizing	0.062	N	0.59	neutral	N	0.495058516	None	None	N
V/E	0.3001	likely_benign	0.3598	ambiguous	-0.151	Destabilizing	0.002	N	0.358	neutral	None	None	None	None	N
V/F	0.1367	likely_benign	0.1803	benign	-0.777	Destabilizing	0.188	N	0.587	neutral	N	0.517916733	None	None	N
V/G	0.1924	likely_benign	0.2161	benign	-1.591	Destabilizing	0.117	N	0.581	neutral	N	0.452750534	None	None	N
V/H	0.4974	ambiguous	0.6122	pathogenic	-1.001	Destabilizing	0.935	D	0.575	neutral	None	None	None	None	N
V/I	0.0589	likely_benign	0.0635	benign	-0.3	Destabilizing	None	N	0.129	neutral	N	0.4743766	None	None	N
V/K	0.3758	ambiguous	0.4708	ambiguous	-0.758	Destabilizing	0.149	N	0.562	neutral	None	None	None	None	N
V/L	0.1261	likely_benign	0.1653	benign	-0.3	Destabilizing	None	N	0.12	neutral	D	0.530229883	None	None	N
V/M	0.0965	likely_benign	0.1117	benign	-0.382	Destabilizing	0.235	N	0.52	neutral	None	None	None	None	N
V/N	0.2179	likely_benign	0.2611	benign	-0.69	Destabilizing	0.38	N	0.61	neutral	None	None	None	None	N
V/P	0.6655	likely_pathogenic	0.7922	pathogenic	-0.571	Destabilizing	0.555	D	0.593	neutral	None	None	None	None	N
V/Q	0.3147	likely_benign	0.3772	ambiguous	-0.693	Destabilizing	0.38	N	0.596	neutral	None	None	None	None	N
V/R	0.2842	likely_benign	0.3784	ambiguous	-0.475	Destabilizing	0.38	N	0.613	neutral	None	None	None	None	N
V/S	0.1237	likely_benign	0.1346	benign	-1.414	Destabilizing	0.081	N	0.573	neutral	None	None	None	None	N
V/T	0.074	likely_benign	0.0806	benign	-1.208	Destabilizing	None	N	0.107	neutral	None	None	None	None	N
V/W	0.6849	likely_pathogenic	0.7894	pathogenic	-0.958	Destabilizing	0.935	D	0.611	neutral	None	None	None	None	N
V/Y	0.4525	ambiguous	0.5422	ambiguous	-0.619	Destabilizing	0.555	D	0.573	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.