TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17159	51700;51701;51702	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
N2AB	15518	46777;46778;46779	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
N2A	14591	43996;43997;43998	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
N2B	8094	24505;24506;24507	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
Novex-1	8219	24880;24881;24882	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
Novex-2	8286	25081;25082;25083	chr2:178609948;178609947;178609946	chr2:179474675;179474674;179474673
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-13
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3099
• 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
P/L	None	None	0.025	N	0.427	0.3	0.470318359215	gnomAD-4.0.0	3.1868E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72443E-06	0	0
P/T	None	None	0.967	N	0.581	0.294	0.334161072951	gnomAD-4.0.0	1.59351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86229E-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
P/A	0.1734	likely_benign	0.2004	benign	-1.022	Destabilizing	0.805	D	0.477	neutral	N	0.440095376	None	None	N
P/C	0.705	likely_pathogenic	0.7514	pathogenic	-0.713	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
P/D	0.9302	likely_pathogenic	0.9348	pathogenic	-1.119	Destabilizing	0.996	D	0.64	neutral	None	None	None	None	N
P/E	0.7255	likely_pathogenic	0.7389	pathogenic	-1.224	Destabilizing	0.987	D	0.617	neutral	None	None	None	None	N
P/F	0.8777	likely_pathogenic	0.8831	pathogenic	-1.305	Destabilizing	0.975	D	0.726	prob.delet.	None	None	None	None	N
P/G	0.7302	likely_pathogenic	0.7588	pathogenic	-1.198	Destabilizing	0.987	D	0.597	neutral	None	None	None	None	N
P/H	0.6061	likely_pathogenic	0.6221	pathogenic	-0.844	Destabilizing	0.999	D	0.655	neutral	N	0.46930487	None	None	N
P/I	0.4184	ambiguous	0.4528	ambiguous	-0.682	Destabilizing	0.653	D	0.638	neutral	None	None	None	None	N
P/K	0.6258	likely_pathogenic	0.6716	pathogenic	-0.726	Destabilizing	0.987	D	0.607	neutral	None	None	None	None	N
P/L	0.304	likely_benign	0.3462	ambiguous	-0.682	Destabilizing	0.025	N	0.427	neutral	N	0.454928756	None	None	N
P/M	0.5706	likely_pathogenic	0.6157	pathogenic	-0.357	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	N
P/N	0.8135	likely_pathogenic	0.8288	pathogenic	-0.461	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	N
P/Q	0.4561	ambiguous	0.481	ambiguous	-0.798	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	N
P/R	0.4546	ambiguous	0.4824	ambiguous	-0.145	Destabilizing	0.983	D	0.679	prob.neutral	N	0.468820773	None	None	N
P/S	0.4251	ambiguous	0.4645	ambiguous	-0.817	Destabilizing	0.967	D	0.588	neutral	N	0.463876313	None	None	N
P/T	0.2316	likely_benign	0.2752	benign	-0.831	Destabilizing	0.967	D	0.581	neutral	N	0.410292544	None	None	N
P/V	0.279	likely_benign	0.3138	benign	-0.761	Destabilizing	0.073	N	0.329	neutral	None	None	None	None	N
P/W	0.9508	likely_pathogenic	0.9489	pathogenic	-1.387	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
P/Y	0.8719	likely_pathogenic	0.8718	pathogenic	-1.066	Destabilizing	0.987	D	0.725	prob.delet.	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.