TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17213	51862;51863;51864	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
N2AB	15572	46939;46940;46941	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
N2A	14645	44158;44159;44160	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
N2B	8148	24667;24668;24669	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
Novex-1	8273	25042;25043;25044	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
Novex-2	8340	25243;25244;25245	chr2:178609786;178609785;178609784	chr2:179474513;179474512;179474511
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-13
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.6497
• 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
E/Q	None	None	0.92	N	0.427	0.178	0.329282125956	gnomAD-4.0.0	8.21406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.0798E-05	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
E/A	0.1445	likely_benign	0.1418	benign	-0.42	Destabilizing	0.826	D	0.426	neutral	N	0.493335215	None	None	N
E/C	0.7651	likely_pathogenic	0.7459	pathogenic	-0.312	Destabilizing	0.999	D	0.464	neutral	None	None	None	None	N
E/D	0.2115	likely_benign	0.1935	benign	-0.567	Destabilizing	0.906	D	0.399	neutral	N	0.473749377	None	None	N
E/F	0.7294	likely_pathogenic	0.716	pathogenic	0.111	Stabilizing	0.997	D	0.449	neutral	None	None	None	None	N
E/G	0.258	likely_benign	0.2374	benign	-0.683	Destabilizing	0.959	D	0.437	neutral	N	0.486754469	None	None	N
E/H	0.4209	ambiguous	0.4095	ambiguous	0.481	Stabilizing	0.997	D	0.387	neutral	None	None	None	None	N
E/I	0.2049	likely_benign	0.2045	benign	0.263	Stabilizing	0.982	D	0.451	neutral	None	None	None	None	N
E/K	0.1273	likely_benign	0.1267	benign	0.279	Stabilizing	0.134	N	0.176	neutral	N	0.4100819	None	None	N
E/L	0.2672	likely_benign	0.2584	benign	0.263	Stabilizing	0.939	D	0.431	neutral	None	None	None	None	N
E/M	0.3533	ambiguous	0.3448	ambiguous	0.239	Stabilizing	0.999	D	0.433	neutral	None	None	None	None	N
E/N	0.3183	likely_benign	0.3003	benign	-0.421	Destabilizing	0.969	D	0.405	neutral	None	None	None	None	N
E/P	0.7602	likely_pathogenic	0.7323	pathogenic	0.056	Stabilizing	0.997	D	0.418	neutral	None	None	None	None	N
E/Q	0.1163	likely_benign	0.1163	benign	-0.309	Destabilizing	0.92	D	0.427	neutral	N	0.474594739	None	None	N
E/R	0.2139	likely_benign	0.216	benign	0.67	Stabilizing	0.884	D	0.403	neutral	None	None	None	None	N
E/S	0.2122	likely_benign	0.2093	benign	-0.556	Destabilizing	0.759	D	0.409	neutral	None	None	None	None	N
E/T	0.1462	likely_benign	0.1479	benign	-0.315	Destabilizing	0.079	N	0.162	neutral	None	None	None	None	N
E/V	0.1231	likely_benign	0.1224	benign	0.056	Stabilizing	0.92	D	0.434	neutral	N	0.449333722	None	None	N
E/W	0.881	likely_pathogenic	0.867	pathogenic	0.391	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	N
E/Y	0.6361	likely_pathogenic	0.6024	pathogenic	0.401	Stabilizing	0.997	D	0.45	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.