TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25631	77116;77117;77118	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
N2AB	23990	72193;72194;72195	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
N2A	23063	69412;69413;69414	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
N2B	16566	49921;49922;49923	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
Novex-1	16691	50296;50297;50298	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
Novex-2	16758	50497;50498;50499	chr2:178569241;178569240;178569239	chr2:179433968;179433967;179433966
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-74
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1555
• Predicted PPI site: I

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
S/C	None	None	0.996	N	0.721	0.389	0.510054698054	gnomAD-4.0.0	2.75659E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.73496E-05	0
S/P	None	None	0.986	N	0.743	0.427	0.296679040009	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0646	likely_benign	0.0692	benign	-0.824	Destabilizing	None	N	0.328	neutral	N	0.470188996	None	None	I
S/C	0.0898	likely_benign	0.1069	benign	-0.445	Destabilizing	0.996	D	0.721	prob.delet.	N	0.487679522	None	None	I
S/D	0.8342	likely_pathogenic	0.8181	pathogenic	-0.268	Destabilizing	0.963	D	0.721	prob.delet.	None	None	None	None	I
S/E	0.8684	likely_pathogenic	0.8728	pathogenic	-0.28	Destabilizing	0.947	D	0.679	prob.neutral	None	None	None	None	I
S/F	0.4546	ambiguous	0.4935	ambiguous	-1.006	Destabilizing	0.996	D	0.767	deleterious	N	0.51467132	None	None	I
S/G	0.1681	likely_benign	0.1816	benign	-1.067	Destabilizing	0.83	D	0.642	neutral	None	None	None	None	I
S/H	0.7372	likely_pathogenic	0.7431	pathogenic	-1.507	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
S/I	0.4069	ambiguous	0.5053	ambiguous	-0.284	Destabilizing	0.994	D	0.766	deleterious	None	None	None	None	I
S/K	0.9526	likely_pathogenic	0.9613	pathogenic	-0.789	Destabilizing	0.98	D	0.688	prob.neutral	None	None	None	None	I
S/L	0.1858	likely_benign	0.2172	benign	-0.284	Destabilizing	0.98	D	0.688	prob.neutral	None	None	None	None	I
S/M	0.3086	likely_benign	0.3584	ambiguous	0.076	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
S/N	0.4355	ambiguous	0.4497	ambiguous	-0.691	Destabilizing	0.752	D	0.727	prob.delet.	None	None	None	None	I
S/P	0.981	likely_pathogenic	0.9853	pathogenic	-0.431	Destabilizing	0.986	D	0.743	deleterious	N	0.521001196	None	None	I
S/Q	0.7888	likely_pathogenic	0.816	pathogenic	-0.851	Destabilizing	0.997	D	0.739	prob.delet.	None	None	None	None	I
S/R	0.9259	likely_pathogenic	0.9382	pathogenic	-0.637	Destabilizing	0.997	D	0.744	deleterious	None	None	None	None	I
S/T	0.1477	likely_benign	0.167	benign	-0.724	Destabilizing	0.318	N	0.64	neutral	N	0.475296032	None	None	I
S/V	0.2495	likely_benign	0.3331	benign	-0.431	Destabilizing	0.9	D	0.69	prob.neutral	None	None	None	None	I
S/W	0.7308	likely_pathogenic	0.7458	pathogenic	-0.969	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
S/Y	0.4847	ambiguous	0.5005	ambiguous	-0.732	Destabilizing	0.999	D	0.765	deleterious	N	0.509644891	None	None	I

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.