TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17202	51829;51830;51831	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
N2AB	15561	46906;46907;46908	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
N2A	14634	44125;44126;44127	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
N2B	8137	24634;24635;24636	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
Novex-1	8262	25009;25010;25011	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
Novex-2	8329	25210;25211;25212	chr2:178609819;178609818;178609817	chr2:179474546;179474545;179474544
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-13
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1208
• 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
V/G	None	None	1.0	N	0.806	0.516	0.812812526149	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79959E-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
V/A	0.842	likely_pathogenic	0.8394	pathogenic	-1.295	Destabilizing	0.999	D	0.605	neutral	N	0.519614952	None	None	N
V/C	0.9397	likely_pathogenic	0.9415	pathogenic	-0.475	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
V/D	0.989	likely_pathogenic	0.9874	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/E	0.9499	likely_pathogenic	0.9468	pathogenic	-1.823	Destabilizing	1.0	D	0.775	deleterious	N	0.502777901	None	None	N
V/F	0.7659	likely_pathogenic	0.7602	pathogenic	-0.749	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
V/G	0.9455	likely_pathogenic	0.9381	pathogenic	-1.841	Destabilizing	1.0	D	0.806	deleterious	N	0.508456596	None	None	N
V/H	0.9806	likely_pathogenic	0.9788	pathogenic	-1.901	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/I	0.1176	likely_benign	0.117	benign	0.246	Stabilizing	0.997	D	0.54	neutral	N	0.475845532	None	None	N
V/K	0.9671	likely_pathogenic	0.9611	pathogenic	-0.905	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
V/L	0.5561	ambiguous	0.5727	pathogenic	0.246	Stabilizing	0.997	D	0.597	neutral	N	0.506283083	None	None	N
V/M	0.6555	likely_pathogenic	0.6686	pathogenic	0.231	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
V/N	0.9585	likely_pathogenic	0.9549	pathogenic	-1.432	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/P	0.9824	likely_pathogenic	0.9775	pathogenic	-0.243	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/Q	0.9342	likely_pathogenic	0.927	pathogenic	-1.139	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/R	0.951	likely_pathogenic	0.9407	pathogenic	-1.098	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/S	0.9107	likely_pathogenic	0.9083	pathogenic	-1.924	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
V/T	0.8452	likely_pathogenic	0.8569	pathogenic	-1.502	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
V/W	0.994	likely_pathogenic	0.9933	pathogenic	-1.394	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/Y	0.968	likely_pathogenic	0.9648	pathogenic	-0.844	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.