TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26127	78604;78605;78606	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
N2AB	24486	73681;73682;73683	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
N2A	23559	70900;70901;70902	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
N2B	17062	51409;51410;51411	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
Novex-1	17187	51784;51785;51786	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
Novex-2	17254	51985;51986;51987	chr2:178567753;178567752;178567751	chr2:179432480;179432479;179432478
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-78
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.153
• 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/T	None	None	1.0	N	0.792	0.544	0.355865052028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
K/A	0.9655	likely_pathogenic	0.9651	pathogenic	-1.475	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/C	0.9125	likely_pathogenic	0.9104	pathogenic	-1.543	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.9965	likely_pathogenic	0.9958	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
K/E	0.9381	likely_pathogenic	0.9352	pathogenic	-1.948	Destabilizing	0.999	D	0.686	prob.neutral	N	0.493271701	None	None	N
K/F	0.9811	likely_pathogenic	0.974	pathogenic	-0.664	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
K/G	0.9736	likely_pathogenic	0.9736	pathogenic	-1.983	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/H	0.8037	likely_pathogenic	0.7928	pathogenic	-1.768	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/I	0.9292	likely_pathogenic	0.9124	pathogenic	-0.012	Destabilizing	1.0	D	0.851	deleterious	N	0.464251987	None	None	N
K/L	0.8903	likely_pathogenic	0.8613	pathogenic	-0.012	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/M	0.7545	likely_pathogenic	0.6994	pathogenic	-0.403	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/N	0.9798	likely_pathogenic	0.9788	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.797	deleterious	N	0.504628007	None	None	N
K/P	0.9992	likely_pathogenic	0.9991	pathogenic	-0.482	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
K/Q	0.6101	likely_pathogenic	0.6238	pathogenic	-1.622	Destabilizing	1.0	D	0.793	deleterious	N	0.476154951	None	None	N
K/R	0.1214	likely_benign	0.1306	benign	-1.035	Destabilizing	0.999	D	0.696	prob.neutral	N	0.431073248	None	None	N
K/S	0.9734	likely_pathogenic	0.9735	pathogenic	-2.551	Highly Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
K/T	0.9136	likely_pathogenic	0.9061	pathogenic	-1.943	Destabilizing	1.0	D	0.792	deleterious	N	0.475875008	None	None	N
K/V	0.894	likely_pathogenic	0.872	pathogenic	-0.482	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/W	0.972	likely_pathogenic	0.9631	pathogenic	-0.776	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/Y	0.9117	likely_pathogenic	0.8887	pathogenic	-0.424	Destabilizing	1.0	D	0.815	deleterious	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.