TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28830	86713;86714;86715	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
N2AB	27189	81790;81791;81792	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
N2A	26262	79009;79010;79011	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
N2B	19765	59518;59519;59520	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
Novex-1	19890	59893;59894;59895	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
Novex-2	19957	60094;60095;60096	chr2:178559644;178559643;178559642	chr2:179424371;179424370;179424369
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-144
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.7606
• Predicted PPI site: I

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	0.012	N	0.289	0.159	0.427713192076	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	None	None	None	N	0.142	0.08	0.277317399466	gnomAD-4.0.0	1.59169E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85883E-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	0.1049	likely_benign	0.101	benign	-0.342	Destabilizing	0.012	N	0.289	neutral	N	0.440415955	None	None	I
V/C	0.5232	ambiguous	0.506	ambiguous	-0.754	Destabilizing	0.676	D	0.279	neutral	None	None	None	None	I
V/D	0.2117	likely_benign	0.2091	benign	-0.248	Destabilizing	0.029	N	0.288	neutral	N	0.48286001	None	None	I
V/E	0.2043	likely_benign	0.2078	benign	-0.361	Destabilizing	0.038	N	0.297	neutral	None	None	None	None	I
V/F	0.1297	likely_benign	0.1253	benign	-0.663	Destabilizing	0.171	N	0.287	neutral	N	0.511644122	None	None	I
V/G	0.1302	likely_benign	0.1258	benign	-0.426	Destabilizing	0.029	N	0.34	neutral	N	0.460503226	None	None	I
V/H	0.333	likely_benign	0.3287	benign	-0.022	Destabilizing	0.001	N	0.38	neutral	None	None	None	None	I
V/I	0.0642	likely_benign	0.0622	benign	-0.266	Destabilizing	None	N	0.142	neutral	N	0.464524966	None	None	I
V/K	0.2241	likely_benign	0.2221	benign	-0.37	Destabilizing	0.038	N	0.295	neutral	None	None	None	None	I
V/L	0.126	likely_benign	0.1214	benign	-0.266	Destabilizing	None	N	0.128	neutral	N	0.479531704	None	None	I
V/M	0.1015	likely_benign	0.097	benign	-0.489	Destabilizing	0.007	N	0.31	neutral	None	None	None	None	I
V/N	0.125	likely_benign	0.1201	benign	-0.17	Destabilizing	None	N	0.322	neutral	None	None	None	None	I
V/P	0.2175	likely_benign	0.1999	benign	-0.261	Destabilizing	0.214	N	0.317	neutral	None	None	None	None	I
V/Q	0.2048	likely_benign	0.2081	benign	-0.376	Destabilizing	0.214	N	0.317	neutral	None	None	None	None	I
V/R	0.2046	likely_benign	0.2005	benign	0.082	Stabilizing	0.214	N	0.305	neutral	None	None	None	None	I
V/S	0.1081	likely_benign	0.1061	benign	-0.499	Destabilizing	None	N	0.301	neutral	None	None	None	None	I
V/T	0.1096	likely_benign	0.1088	benign	-0.514	Destabilizing	0.016	N	0.241	neutral	None	None	None	None	I
V/W	0.7021	likely_pathogenic	0.6763	pathogenic	-0.733	Destabilizing	0.864	D	0.281	neutral	None	None	None	None	I
V/Y	0.3682	ambiguous	0.3461	ambiguous	-0.445	Destabilizing	0.214	N	0.285	neutral	None	None	None	None	I

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.