TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5302	16129;16130;16131	chr2:178733389;178733388;178733387	chr2:179598116;179598115;179598114
N2AB	4985	15178;15179;15180	chr2:178733389;178733388;178733387	chr2:179598116;179598115;179598114
N2A	4058	12397;12398;12399	chr2:178733389;178733388;178733387	chr2:179598116;179598115;179598114
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-36
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.697
• 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	0.213	N	0.417	0.288	0.625243557465	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
V/I	rs1410470675	None	0.001	N	0.166	0.045	0.28058544554	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1410470675	None	0.001	N	0.166	0.045	0.28058544554	gnomAD-4.0.0	2.5624E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78618E-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	0.1031	likely_benign	0.1218	benign	-0.505	Destabilizing	0.001	N	0.116	neutral	N	0.45718603	None	None	N
V/C	0.6936	likely_pathogenic	0.7597	pathogenic	-0.895	Destabilizing	0.951	D	0.343	neutral	None	None	None	None	N
V/D	0.2731	likely_benign	0.3239	benign	-0.366	Destabilizing	0.213	N	0.417	neutral	N	0.489227862	None	None	N
V/E	0.2295	likely_benign	0.2627	benign	-0.437	Destabilizing	0.01	N	0.285	neutral	None	None	None	None	N
V/F	0.1374	likely_benign	0.1628	benign	-0.63	Destabilizing	0.655	D	0.359	neutral	N	0.510702151	None	None	N
V/G	0.1571	likely_benign	0.1832	benign	-0.626	Destabilizing	0.213	N	0.395	neutral	N	0.494365855	None	None	N
V/H	0.4164	ambiguous	0.4661	ambiguous	-0.002	Destabilizing	0.983	D	0.368	neutral	None	None	None	None	N
V/I	0.0794	likely_benign	0.0893	benign	-0.307	Destabilizing	0.001	N	0.166	neutral	N	0.474684616	None	None	N
V/K	0.2716	likely_benign	0.2883	benign	-0.509	Destabilizing	0.418	N	0.389	neutral	None	None	None	None	N
V/L	0.1312	likely_benign	0.1623	benign	-0.307	Destabilizing	0.037	N	0.229	neutral	N	0.499379932	None	None	N
V/M	0.1216	likely_benign	0.1469	benign	-0.687	Destabilizing	0.716	D	0.309	neutral	None	None	None	None	N
V/N	0.204	likely_benign	0.253	benign	-0.449	Destabilizing	0.716	D	0.415	neutral	None	None	None	None	N
V/P	0.269	likely_benign	0.3332	benign	-0.344	Destabilizing	0.002	N	0.293	neutral	None	None	None	None	N
V/Q	0.2428	likely_benign	0.261	benign	-0.594	Destabilizing	0.716	D	0.387	neutral	None	None	None	None	N
V/R	0.2461	likely_benign	0.2483	benign	-0.06	Destabilizing	0.716	D	0.411	neutral	None	None	None	None	N
V/S	0.138	likely_benign	0.1672	benign	-0.795	Destabilizing	0.129	N	0.388	neutral	None	None	None	None	N
V/T	0.1255	likely_benign	0.1398	benign	-0.762	Destabilizing	0.004	N	0.135	neutral	None	None	None	None	N
V/W	0.6792	likely_pathogenic	0.7571	pathogenic	-0.702	Destabilizing	0.983	D	0.409	neutral	None	None	None	None	N
V/Y	0.4147	ambiguous	0.4774	ambiguous	-0.434	Destabilizing	0.836	D	0.343	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.