TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26135	78628;78629;78630	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
N2AB	24494	73705;73706;73707	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
N2A	23567	70924;70925;70926	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
N2B	17070	51433;51434;51435	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
Novex-1	17195	51808;51809;51810	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
Novex-2	17262	52009;52010;52011	chr2:178567729;178567728;178567727	chr2:179432456;179432455;179432454
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-78
• Domain position: 48
• Structural Position: 65
• Q(SASA): 0.246
• 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
W/G	None	None	0.983	D	0.623	0.521	0.574263788935	gnomAD-4.0.0	6.84771E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00208E-07	0	0
W/R	None	None	0.994	D	0.744	0.511	0.627131723059	gnomAD-4.0.0	1.36954E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80042E-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
W/A	0.9973	likely_pathogenic	0.997	pathogenic	-2.902	Highly Destabilizing	0.845	D	0.628	neutral	None	None	None	None	N
W/C	0.9986	likely_pathogenic	0.9983	pathogenic	-1.12	Destabilizing	0.056	N	0.384	neutral	D	0.526266391	None	None	N
W/D	0.9993	likely_pathogenic	0.9992	pathogenic	-1.618	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
W/E	0.9995	likely_pathogenic	0.9994	pathogenic	-1.558	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	N
W/F	0.7872	likely_pathogenic	0.7843	pathogenic	-1.804	Destabilizing	0.987	D	0.637	neutral	None	None	None	None	N
W/G	0.9902	likely_pathogenic	0.9894	pathogenic	-3.088	Highly Destabilizing	0.983	D	0.623	neutral	D	0.525505922	None	None	N
W/H	0.9965	likely_pathogenic	0.9959	pathogenic	-1.393	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
W/I	0.9959	likely_pathogenic	0.9954	pathogenic	-2.234	Highly Destabilizing	0.975	D	0.749	deleterious	None	None	None	None	N
W/K	0.9997	likely_pathogenic	0.9997	pathogenic	-1.502	Destabilizing	0.987	D	0.743	deleterious	None	None	None	None	N
W/L	0.9876	likely_pathogenic	0.9858	pathogenic	-2.234	Highly Destabilizing	0.805	D	0.583	neutral	N	0.517237036	None	None	N
W/M	0.9963	likely_pathogenic	0.9959	pathogenic	-1.618	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
W/N	0.9989	likely_pathogenic	0.9988	pathogenic	-1.82	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
W/P	0.998	likely_pathogenic	0.9976	pathogenic	-2.472	Highly Destabilizing	0.996	D	0.734	prob.delet.	None	None	None	None	N
W/Q	0.9997	likely_pathogenic	0.9997	pathogenic	-1.85	Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
W/R	0.9995	likely_pathogenic	0.9994	pathogenic	-0.876	Destabilizing	0.994	D	0.744	deleterious	D	0.529607299	None	None	N
W/S	0.9957	likely_pathogenic	0.9949	pathogenic	-2.222	Highly Destabilizing	0.967	D	0.743	deleterious	N	0.515528742	None	None	N
W/T	0.998	likely_pathogenic	0.9977	pathogenic	-2.12	Highly Destabilizing	0.975	D	0.654	neutral	None	None	None	None	N
W/V	0.9957	likely_pathogenic	0.9953	pathogenic	-2.472	Highly Destabilizing	0.975	D	0.722	prob.delet.	None	None	None	None	N
W/Y	0.9329	likely_pathogenic	0.9286	pathogenic	-1.644	Destabilizing	0.996	D	0.621	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.