TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8465	25618;25619;25620	chr2:178717341;178717340;178717339	chr2:179582068;179582067;179582066
N2AB	8148	24667;24668;24669	chr2:178717341;178717340;178717339	chr2:179582068;179582067;179582066
N2A	7221	21886;21887;21888	chr2:178717341;178717340;178717339	chr2:179582068;179582067;179582066
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-70
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.4595
• 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/G	None	None	0.928	N	0.416	0.55	0.857228785163	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

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	0.1219	likely_benign	0.1163	benign	-0.854	Destabilizing	0.184	N	0.291	neutral	N	0.500104551	None	None	N
V/C	0.7832	likely_pathogenic	0.7017	pathogenic	-0.823	Destabilizing	0.983	D	0.349	neutral	None	None	None	None	N
V/D	0.3331	likely_benign	0.2793	benign	0.011	Stabilizing	0.862	D	0.444	neutral	None	None	None	None	N
V/E	0.2177	likely_benign	0.1897	benign	0.002	Stabilizing	0.098	N	0.377	neutral	N	0.501882297	None	None	N
V/F	0.1578	likely_benign	0.1436	benign	-0.557	Destabilizing	0.824	D	0.384	neutral	None	None	None	None	N
V/G	0.193	likely_benign	0.1665	benign	-1.134	Destabilizing	0.928	D	0.416	neutral	N	0.51166844	None	None	N
V/H	0.4784	ambiguous	0.405	ambiguous	-0.577	Destabilizing	0.963	D	0.403	neutral	None	None	None	None	N
V/I	0.0745	likely_benign	0.0738	benign	-0.214	Destabilizing	None	N	0.093	neutral	N	0.469242926	None	None	N
V/K	0.2439	likely_benign	0.2059	benign	-0.626	Destabilizing	0.239	N	0.391	neutral	None	None	None	None	N
V/L	0.1438	likely_benign	0.1312	benign	-0.214	Destabilizing	None	N	0.087	neutral	N	0.493138506	None	None	N
V/M	0.0981	likely_benign	0.0968	benign	-0.375	Destabilizing	0.771	D	0.391	neutral	None	None	None	None	N
V/N	0.2457	likely_benign	0.2156	benign	-0.476	Destabilizing	0.399	N	0.439	neutral	None	None	None	None	N
V/P	0.7332	likely_pathogenic	0.6714	pathogenic	-0.39	Destabilizing	0.669	D	0.414	neutral	None	None	None	None	N
V/Q	0.2332	likely_benign	0.202	benign	-0.561	Destabilizing	0.039	N	0.341	neutral	None	None	None	None	N
V/R	0.2158	likely_benign	0.1805	benign	-0.266	Destabilizing	0.824	D	0.433	neutral	None	None	None	None	N
V/S	0.173	likely_benign	0.1523	benign	-1.071	Destabilizing	0.419	N	0.369	neutral	None	None	None	None	N
V/T	0.1167	likely_benign	0.1115	benign	-0.953	Destabilizing	0.226	N	0.251	neutral	None	None	None	None	N
V/W	0.7515	likely_pathogenic	0.6733	pathogenic	-0.696	Destabilizing	0.997	D	0.485	neutral	None	None	None	None	N
V/Y	0.5341	ambiguous	0.4593	ambiguous	-0.38	Destabilizing	0.905	D	0.389	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.