TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23332	70219;70220;70221	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
N2AB	21691	65296;65297;65298	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
N2A	20764	62515;62516;62517	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
N2B	14267	43024;43025;43026	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
Novex-1	14392	43399;43400;43401	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
Novex-2	14459	43600;43601;43602	chr2:178576138;178576137;178576136	chr2:179440865;179440864;179440863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-57
• Domain position: 93
• Structural Position: 125
• Q(SASA): 1.0687
• 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
D/H	None	None	0.087	N	0.288	0.062	0.132336055621	gnomAD-4.0.0	1.36872E-06	None	None	None	None	I	None	2.98918E-05	0	None	0	0	None	0	0	8.99607E-07	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
D/A	0.0993	likely_benign	0.0923	benign	-0.268	Destabilizing	0.002	N	0.281	neutral	N	0.487068177	None	None	I
D/C	0.381	ambiguous	0.3816	ambiguous	-0.094	Destabilizing	0.747	D	0.272	neutral	None	None	None	None	I
D/E	0.1165	likely_benign	0.1119	benign	-0.338	Destabilizing	0.002	N	0.163	neutral	N	0.406028449	None	None	I
D/F	0.4562	ambiguous	0.4468	ambiguous	-0.156	Destabilizing	0.439	N	0.427	neutral	None	None	None	None	I
D/G	0.101	likely_benign	0.1062	benign	-0.485	Destabilizing	None	N	0.073	neutral	N	0.418459028	None	None	I
D/H	0.1691	likely_benign	0.1707	benign	-0.016	Destabilizing	0.087	N	0.288	neutral	N	0.488281686	None	None	I
D/I	0.31	likely_benign	0.2877	benign	0.26	Stabilizing	0.204	N	0.492	neutral	None	None	None	None	I
D/K	0.2399	likely_benign	0.2414	benign	0.078	Stabilizing	None	N	0.081	neutral	None	None	None	None	I
D/L	0.2796	likely_benign	0.2707	benign	0.26	Stabilizing	0.035	N	0.438	neutral	None	None	None	None	I
D/M	0.3991	ambiguous	0.3879	ambiguous	0.333	Stabilizing	0.439	N	0.308	neutral	None	None	None	None	I
D/N	0.0613	likely_benign	0.0649	benign	-0.166	Destabilizing	None	N	0.049	neutral	N	0.468829133	None	None	I
D/P	0.5477	ambiguous	0.487	ambiguous	0.107	Stabilizing	0.068	N	0.398	neutral	None	None	None	None	I
D/Q	0.1982	likely_benign	0.1946	benign	-0.121	Destabilizing	0.001	N	0.232	neutral	None	None	None	None	I
D/R	0.2784	likely_benign	0.2768	benign	0.317	Stabilizing	0.007	N	0.345	neutral	None	None	None	None	I
D/S	0.0811	likely_benign	0.0784	benign	-0.309	Destabilizing	None	N	0.077	neutral	None	None	None	None	I
D/T	0.1474	likely_benign	0.1363	benign	-0.146	Destabilizing	0.007	N	0.254	neutral	None	None	None	None	I
D/V	0.1825	likely_benign	0.1662	benign	0.107	Stabilizing	0.026	N	0.53	neutral	N	0.507310164	None	None	I
D/W	0.8134	likely_pathogenic	0.8117	pathogenic	-0.036	Destabilizing	0.747	D	0.287	neutral	None	None	None	None	I
D/Y	0.1732	likely_benign	0.1744	benign	0.067	Stabilizing	0.371	N	0.47	neutral	N	0.507136805	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.