TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34428	103507;103508;103509	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
N2AB	32787	98584;98585;98586	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
N2A	31860	95803;95804;95805	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
N2B	25363	76312;76313;76314	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
Novex-1	25488	76687;76688;76689	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
Novex-2	25555	76888;76889;76890	chr2:178533333;178533332;178533331	chr2:179398060;179398059;179398058
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: Ig-162
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.3286
• 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	0.217	N	0.419	0.291	0.335414705075	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85767E-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	0.2435	likely_benign	0.2137	benign	-1.03	Destabilizing	0.994	D	0.387	neutral	N	0.484367094	None	None	N
P/C	0.9002	likely_pathogenic	0.8731	pathogenic	-0.82	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
P/D	0.9348	likely_pathogenic	0.9125	pathogenic	-0.761	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
P/E	0.7038	likely_pathogenic	0.6428	pathogenic	-0.857	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
P/F	0.9104	likely_pathogenic	0.8635	pathogenic	-1.089	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
P/G	0.8458	likely_pathogenic	0.7979	pathogenic	-1.218	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
P/H	0.7155	likely_pathogenic	0.635	pathogenic	-0.671	Destabilizing	1.0	D	0.659	neutral	N	0.49300798	None	None	N
P/I	0.5994	likely_pathogenic	0.512	ambiguous	-0.664	Destabilizing	0.995	D	0.628	neutral	None	None	None	None	N
P/K	0.7908	likely_pathogenic	0.7182	pathogenic	-0.807	Destabilizing	1.0	D	0.576	neutral	None	None	None	None	N
P/L	0.2649	likely_benign	0.2313	benign	-0.664	Destabilizing	0.217	N	0.419	neutral	N	0.468242848	None	None	N
P/M	0.6745	likely_pathogenic	0.5921	pathogenic	-0.501	Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
P/N	0.9118	likely_pathogenic	0.8708	pathogenic	-0.526	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
P/Q	0.5857	likely_pathogenic	0.5096	ambiguous	-0.822	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
P/R	0.6142	likely_pathogenic	0.5472	ambiguous	-0.179	Destabilizing	0.999	D	0.647	neutral	N	0.486252606	None	None	N
P/S	0.5485	ambiguous	0.4797	ambiguous	-0.954	Destabilizing	0.999	D	0.513	neutral	N	0.494853447	None	None	N
P/T	0.3962	ambiguous	0.3335	benign	-0.951	Destabilizing	0.998	D	0.507	neutral	N	0.520981255	None	None	N
P/V	0.4415	ambiguous	0.3738	ambiguous	-0.75	Destabilizing	0.983	D	0.475	neutral	None	None	None	None	N
P/W	0.9444	likely_pathogenic	0.9215	pathogenic	-1.125	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
P/Y	0.9002	likely_pathogenic	0.8544	pathogenic	-0.858	Destabilizing	1.0	D	0.719	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.