TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19280	58063;58064;58065	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
N2AB	17639	53140;53141;53142	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
N2A	16712	50359;50360;50361	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
N2B	10215	30868;30869;30870	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
Novex-1	10340	31243;31244;31245	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
Novex-2	10407	31444;31445;31446	chr2:178595516;178595515;178595514	chr2:179460243;179460242;179460241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-27
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.1313
• 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/K	rs566966765	0.762	0.058	N	0.647	0.184	0.252681307341	gnomAD-2.1.1	6.25E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.58E-05	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	0.3417	ambiguous	0.3175	benign	-0.187	Destabilizing	0.058	N	0.607	neutral	N	0.469850641	None	None	N
E/C	0.8987	likely_pathogenic	0.8857	pathogenic	0.016	Stabilizing	0.869	D	0.548	neutral	None	None	None	None	N
E/D	0.0489	likely_benign	0.0625	benign	-0.206	Destabilizing	None	N	0.094	neutral	N	0.381748867	None	None	N
E/F	0.8812	likely_pathogenic	0.8824	pathogenic	-0.18	Destabilizing	0.637	D	0.529	neutral	None	None	None	None	N
E/G	0.374	ambiguous	0.364	ambiguous	-0.353	Destabilizing	0.058	N	0.567	neutral	N	0.489476551	None	None	N
E/H	0.6708	likely_pathogenic	0.6749	pathogenic	0.147	Stabilizing	0.366	N	0.483	neutral	None	None	None	None	N
E/I	0.7108	likely_pathogenic	0.7005	pathogenic	0.201	Stabilizing	0.366	N	0.607	neutral	None	None	None	None	N
E/K	0.5124	ambiguous	0.507	ambiguous	0.411	Stabilizing	0.058	N	0.647	neutral	N	0.504963292	None	None	N
E/L	0.6518	likely_pathogenic	0.652	pathogenic	0.201	Stabilizing	0.221	N	0.613	neutral	None	None	None	None	N
E/M	0.7563	likely_pathogenic	0.7362	pathogenic	0.187	Stabilizing	0.869	D	0.541	neutral	None	None	None	None	N
E/N	0.2249	likely_benign	0.2394	benign	0.219	Stabilizing	0.039	N	0.593	neutral	None	None	None	None	N
E/P	0.6046	likely_pathogenic	0.6284	pathogenic	0.092	Stabilizing	0.141	N	0.673	prob.neutral	None	None	None	None	N
E/Q	0.3526	ambiguous	0.323	benign	0.234	Stabilizing	0.058	N	0.61	neutral	N	0.495362374	None	None	N
E/R	0.6603	likely_pathogenic	0.6578	pathogenic	0.597	Stabilizing	0.221	N	0.508	neutral	None	None	None	None	N
E/S	0.3108	likely_benign	0.2925	benign	0.038	Stabilizing	0.016	N	0.578	neutral	None	None	None	None	N
E/T	0.4674	ambiguous	0.447	ambiguous	0.171	Stabilizing	0.075	N	0.619	neutral	None	None	None	None	N
E/V	0.5141	ambiguous	0.4884	ambiguous	0.092	Stabilizing	0.303	N	0.621	neutral	N	0.506350159	None	None	N
E/W	0.9526	likely_pathogenic	0.9542	pathogenic	-0.089	Destabilizing	0.869	D	0.607	neutral	None	None	None	None	N
E/Y	0.7181	likely_pathogenic	0.7361	pathogenic	0.055	Stabilizing	0.637	D	0.566	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.