TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23835	71728;71729;71730	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
N2AB	22194	66805;66806;66807	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
N2A	21267	64024;64025;64026	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
N2B	14770	44533;44534;44535	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
Novex-1	14895	44908;44909;44910	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
Novex-2	14962	45109;45110;45111	chr2:178574629;178574628;178574627	chr2:179439356;179439355;179439354
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: Fn3-61
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3419
• 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
V/L	None	None	0.075	N	0.351	0.098	0.37568098594	gnomAD-4.0.0	1.59281E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86076E-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	0.3741	ambiguous	0.3299	benign	-1.699	Destabilizing	0.517	D	0.563	neutral	N	0.495951446	None	None	I
V/C	0.8321	likely_pathogenic	0.8026	pathogenic	-1.238	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	I
V/D	0.8867	likely_pathogenic	0.8659	pathogenic	-1.491	Destabilizing	0.987	D	0.783	deleterious	None	None	None	None	I
V/E	0.8379	likely_pathogenic	0.8155	pathogenic	-1.453	Destabilizing	0.983	D	0.759	deleterious	N	0.511814619	None	None	I
V/F	0.5139	ambiguous	0.4387	ambiguous	-1.284	Destabilizing	0.923	D	0.707	prob.neutral	None	None	None	None	I
V/G	0.5548	ambiguous	0.4878	ambiguous	-2.074	Highly Destabilizing	0.949	D	0.762	deleterious	N	0.513434007	None	None	I
V/H	0.9381	likely_pathogenic	0.9256	pathogenic	-1.613	Destabilizing	0.996	D	0.77	deleterious	None	None	None	None	I
V/I	0.0771	likely_benign	0.0764	benign	-0.747	Destabilizing	0.003	N	0.175	neutral	N	0.463745814	None	None	I
V/K	0.8831	likely_pathogenic	0.8605	pathogenic	-1.403	Destabilizing	0.961	D	0.763	deleterious	None	None	None	None	I
V/L	0.379	ambiguous	0.3065	benign	-0.747	Destabilizing	0.075	N	0.351	neutral	N	0.521561966	None	None	I
V/M	0.3054	likely_benign	0.2598	benign	-0.59	Destabilizing	0.923	D	0.609	neutral	None	None	None	None	I
V/N	0.6783	likely_pathogenic	0.6548	pathogenic	-1.225	Destabilizing	0.987	D	0.791	deleterious	None	None	None	None	I
V/P	0.598	likely_pathogenic	0.5536	ambiguous	-1.03	Destabilizing	0.987	D	0.764	deleterious	None	None	None	None	I
V/Q	0.8527	likely_pathogenic	0.8159	pathogenic	-1.337	Destabilizing	0.987	D	0.764	deleterious	None	None	None	None	I
V/R	0.8649	likely_pathogenic	0.8389	pathogenic	-0.933	Destabilizing	0.961	D	0.794	deleterious	None	None	None	None	I
V/S	0.6092	likely_pathogenic	0.5626	ambiguous	-1.811	Destabilizing	0.961	D	0.709	prob.delet.	None	None	None	None	I
V/T	0.4687	ambiguous	0.4549	ambiguous	-1.645	Destabilizing	0.775	D	0.587	neutral	None	None	None	None	I
V/W	0.9696	likely_pathogenic	0.9589	pathogenic	-1.492	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	I
V/Y	0.8648	likely_pathogenic	0.8358	pathogenic	-1.203	Destabilizing	0.961	D	0.717	prob.delet.	None	None	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.