TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10160	30703;30704;30705	chr2:178702201;178702200;178702199	chr2:179566928;179566927;179566926
N2AB	9843	29752;29753;29754	chr2:178702201;178702200;178702199	chr2:179566928;179566927;179566926
N2A	8916	26971;26972;26973	chr2:178702201;178702200;178702199	chr2:179566928;179566927;179566926
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-86
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.0844
• 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
R/K	None	None	0.022	None	0.253	0.06	0.209622950755	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-06	0	0
R/S	None	None	0.454	None	0.591	0.152	0.269558022972	gnomAD-4.0.0	1.59085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85745E-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
R/A	0.9304	likely_pathogenic	0.9518	pathogenic	-0.556	Destabilizing	0.525	D	0.557	neutral	None	None	None	None	N
R/C	0.7314	likely_pathogenic	0.801	pathogenic	-0.653	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
R/D	0.985	likely_pathogenic	0.99	pathogenic	0.025	Stabilizing	0.842	D	0.557	neutral	None	None	None	None	N
R/E	0.8166	likely_pathogenic	0.873	pathogenic	0.131	Stabilizing	0.688	D	0.595	neutral	None	None	None	None	N
R/F	0.9339	likely_pathogenic	0.9544	pathogenic	-0.514	Destabilizing	0.974	D	0.685	prob.neutral	None	None	None	None	N
R/G	0.9373	likely_pathogenic	0.9552	pathogenic	-0.824	Destabilizing	0.801	D	0.579	neutral	None	None	None	None	N
R/H	0.3706	ambiguous	0.4333	ambiguous	-1.092	Destabilizing	0.991	D	0.548	neutral	None	None	None	None	N
R/I	0.7182	likely_pathogenic	0.8222	pathogenic	0.146	Stabilizing	0.934	D	0.678	prob.neutral	None	None	None	None	N
R/K	0.2993	likely_benign	0.3914	ambiguous	-0.587	Destabilizing	0.022	N	0.253	neutral	None	None	None	None	N
R/L	0.7383	likely_pathogenic	0.8096	pathogenic	0.146	Stabilizing	0.728	D	0.587	neutral	None	None	None	None	N
R/M	0.8373	likely_pathogenic	0.8989	pathogenic	-0.269	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
R/N	0.9654	likely_pathogenic	0.978	pathogenic	-0.206	Destabilizing	0.842	D	0.574	neutral	None	None	None	None	N
R/P	0.9901	likely_pathogenic	0.9936	pathogenic	-0.067	Destabilizing	0.974	D	0.603	neutral	None	None	None	None	N
R/Q	0.3536	ambiguous	0.4121	ambiguous	-0.348	Destabilizing	0.842	D	0.564	neutral	None	None	None	None	N
R/S	0.9381	likely_pathogenic	0.9549	pathogenic	-0.871	Destabilizing	0.454	N	0.591	neutral	None	None	None	None	N
R/T	0.7409	likely_pathogenic	0.8312	pathogenic	-0.597	Destabilizing	0.051	N	0.37	neutral	None	None	None	None	N
R/V	0.7598	likely_pathogenic	0.8377	pathogenic	-0.067	Destabilizing	0.728	D	0.58	neutral	None	None	None	None	N
R/W	0.679	likely_pathogenic	0.738	pathogenic	-0.288	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
R/Y	0.8752	likely_pathogenic	0.9133	pathogenic	0.033	Stabilizing	0.991	D	0.622	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.