TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3107	9544;9545;9546	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
N2AB	3107	9544;9545;9546	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
N2A	3107	9544;9545;9546	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
N2B	3061	9406;9407;9408	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
Novex-1	3061	9406;9407;9408	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
Novex-2	3061	9406;9407;9408	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636
Novex-3	3107	9544;9545;9546	chr2:178767911;178767910;178767909	chr2:179632638;179632637;179632636

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-21
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.683
• 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
K/E	rs764095381	0.362	0.454	N	0.427	0.248	0.319970858106	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
K/E	rs764095381	0.362	0.454	N	0.427	0.248	0.319970858106	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
K/E	rs764095381	0.362	0.454	N	0.427	0.248	0.319970858106	gnomAD-4.0.0	5.12262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.56732E-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
K/A	0.7115	likely_pathogenic	0.7682	pathogenic	-0.332	Destabilizing	0.525	D	0.478	neutral	None	None	None	None	N
K/C	0.9139	likely_pathogenic	0.9352	pathogenic	-0.3	Destabilizing	0.998	D	0.532	neutral	None	None	None	None	N
K/D	0.8715	likely_pathogenic	0.9036	pathogenic	-0.172	Destabilizing	0.842	D	0.494	neutral	None	None	None	None	N
K/E	0.4123	ambiguous	0.4816	ambiguous	-0.1	Destabilizing	0.454	N	0.427	neutral	N	0.434129062	None	None	N
K/F	0.971	likely_pathogenic	0.9779	pathogenic	-0.151	Destabilizing	0.991	D	0.545	neutral	None	None	None	None	N
K/G	0.7827	likely_pathogenic	0.8398	pathogenic	-0.669	Destabilizing	0.688	D	0.554	neutral	None	None	None	None	N
K/H	0.581	likely_pathogenic	0.6381	pathogenic	-1.134	Destabilizing	0.974	D	0.504	neutral	None	None	None	None	N
K/I	0.8037	likely_pathogenic	0.8502	pathogenic	0.518	Stabilizing	0.974	D	0.539	neutral	None	None	None	None	N
K/L	0.7863	likely_pathogenic	0.8311	pathogenic	0.518	Stabilizing	0.842	D	0.541	neutral	None	None	None	None	N
K/M	0.5813	likely_pathogenic	0.646	pathogenic	0.458	Stabilizing	0.989	D	0.508	neutral	N	0.512123715	None	None	N
K/N	0.7099	likely_pathogenic	0.7853	pathogenic	-0.222	Destabilizing	0.801	D	0.44	neutral	N	0.445140607	None	None	N
K/P	0.9378	likely_pathogenic	0.9477	pathogenic	0.265	Stabilizing	0.915	D	0.505	neutral	None	None	None	None	N
K/Q	0.229	likely_benign	0.2667	benign	-0.357	Destabilizing	0.051	N	0.211	neutral	N	0.41211662	None	None	N
K/R	0.1026	likely_benign	0.1135	benign	-0.538	Destabilizing	0.012	N	0.208	neutral	N	0.451951631	None	None	N
K/S	0.7194	likely_pathogenic	0.7832	pathogenic	-0.786	Destabilizing	0.08	N	0.21	neutral	None	None	None	None	N
K/T	0.4048	ambiguous	0.4663	ambiguous	-0.527	Destabilizing	0.669	D	0.481	neutral	N	0.431896714	None	None	N
K/V	0.741	likely_pathogenic	0.7823	pathogenic	0.265	Stabilizing	0.915	D	0.547	neutral	None	None	None	None	N
K/W	0.9378	likely_pathogenic	0.9492	pathogenic	-0.065	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	N
K/Y	0.8982	likely_pathogenic	0.9197	pathogenic	0.237	Stabilizing	0.991	D	0.551	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.