TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34162	102709;102710;102711	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
N2AB	32521	97786;97787;97788	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
N2A	31594	95005;95006;95007	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
N2B	25097	75514;75515;75516	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
Novex-1	25222	75889;75890;75891	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
Novex-2	25289	76090;76091;76092	chr2:178534131;178534130;178534129	chr2:179398858;179398857;179398856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-160
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.2844
• 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
Y/H	rs1439821574	-0.6	1.0	N	0.76	0.522	0.478605750892	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	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
Y/A	0.7131	likely_pathogenic	0.6254	pathogenic	-1.473	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
Y/C	0.3976	ambiguous	0.3947	ambiguous	-0.101	Destabilizing	1.0	D	0.763	deleterious	N	0.495403247	None	None	N
Y/D	0.6345	likely_pathogenic	0.5476	ambiguous	0.102	Stabilizing	1.0	D	0.77	deleterious	N	0.513238845	None	None	N
Y/E	0.8561	likely_pathogenic	0.7996	pathogenic	0.119	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
Y/F	0.1435	likely_benign	0.1401	benign	-0.76	Destabilizing	0.999	D	0.557	neutral	N	0.490922133	None	None	N
Y/G	0.6942	likely_pathogenic	0.6127	pathogenic	-1.735	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
Y/H	0.3754	ambiguous	0.3022	benign	-0.539	Destabilizing	1.0	D	0.76	deleterious	N	0.49873354	None	None	N
Y/I	0.7598	likely_pathogenic	0.7039	pathogenic	-0.738	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
Y/K	0.7949	likely_pathogenic	0.7025	pathogenic	-0.367	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
Y/L	0.7222	likely_pathogenic	0.686	pathogenic	-0.738	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
Y/M	0.8195	likely_pathogenic	0.7863	pathogenic	-0.349	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
Y/N	0.4209	ambiguous	0.334	benign	-0.493	Destabilizing	1.0	D	0.783	deleterious	N	0.491959496	None	None	N
Y/P	0.8699	likely_pathogenic	0.8079	pathogenic	-0.969	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
Y/Q	0.778	likely_pathogenic	0.6897	pathogenic	-0.472	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
Y/R	0.6263	likely_pathogenic	0.5236	ambiguous	-0.014	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
Y/S	0.4166	ambiguous	0.3292	benign	-0.947	Destabilizing	1.0	D	0.762	deleterious	N	0.481550501	None	None	N
Y/T	0.6885	likely_pathogenic	0.6124	pathogenic	-0.837	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
Y/V	0.6383	likely_pathogenic	0.5778	pathogenic	-0.969	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
Y/W	0.5798	likely_pathogenic	0.5488	ambiguous	-0.685	Destabilizing	1.0	D	0.739	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.