TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6426	19501;19502;19503	chr2:178728650;178728649;178728648	chr2:179593377;179593376;179593375
N2AB	6109	18550;18551;18552	chr2:178728650;178728649;178728648	chr2:179593377;179593376;179593375
N2A	5182	15769;15770;15771	chr2:178728650;178728649;178728648	chr2:179593377;179593376;179593375
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-48
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.4111
• 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/F	rs778339438	None	0.351	N	0.453	0.278	0.784326782449	gnomAD-4.0.0	1.16351E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52934E-05	0	0
V/I	rs778339438	None	0.003	N	0.217	0.06	0.551508998025	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/I	rs778339438	None	0.003	N	0.217	0.06	0.551508998025	gnomAD-4.0.0	3.42207E-06	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	3.59844E-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	0.1827	likely_benign	0.138	benign	-0.386	Destabilizing	0.047	N	0.205	neutral	N	0.459905793	None	None	N
V/C	0.781	likely_pathogenic	0.7178	pathogenic	-0.666	Destabilizing	0.94	D	0.389	neutral	None	None	None	None	N
V/D	0.4255	ambiguous	0.2539	benign	-0.44	Destabilizing	0.351	N	0.475	neutral	N	0.489228622	None	None	N
V/E	0.2937	likely_benign	0.1871	benign	-0.533	Destabilizing	0.129	N	0.409	neutral	None	None	None	None	N
V/F	0.1346	likely_benign	0.1107	benign	-0.616	Destabilizing	0.351	N	0.453	neutral	N	0.512990916	None	None	N
V/G	0.2499	likely_benign	0.1789	benign	-0.504	Destabilizing	0.523	D	0.489	neutral	N	0.475029961	None	None	N
V/H	0.5118	ambiguous	0.399	ambiguous	-0.055	Destabilizing	0.836	D	0.431	neutral	None	None	None	None	N
V/I	0.0788	likely_benign	0.0735	benign	-0.21	Destabilizing	0.003	N	0.217	neutral	N	0.456617558	None	None	N
V/K	0.3369	likely_benign	0.2322	benign	-0.455	Destabilizing	0.01	N	0.25	neutral	None	None	None	None	N
V/L	0.133	likely_benign	0.1069	benign	-0.21	Destabilizing	0.001	N	0.145	neutral	N	0.470989578	None	None	N
V/M	0.1098	likely_benign	0.0982	benign	-0.497	Destabilizing	0.01	N	0.195	neutral	None	None	None	None	N
V/N	0.2955	likely_benign	0.2053	benign	-0.252	Destabilizing	0.593	D	0.469	neutral	None	None	None	None	N
V/P	0.4756	ambiguous	0.3565	ambiguous	-0.237	Destabilizing	0.816	D	0.472	neutral	None	None	None	None	N
V/Q	0.2726	likely_benign	0.2088	benign	-0.446	Destabilizing	0.012	N	0.217	neutral	None	None	None	None	N
V/R	0.293	likely_benign	0.22	benign	0.006	Stabilizing	0.264	N	0.468	neutral	None	None	None	None	N
V/S	0.1896	likely_benign	0.1426	benign	-0.553	Destabilizing	0.228	N	0.437	neutral	None	None	None	None	N
V/T	0.1657	likely_benign	0.1338	benign	-0.548	Destabilizing	0.228	N	0.235	neutral	None	None	None	None	N
V/W	0.7308	likely_pathogenic	0.6309	pathogenic	-0.717	Destabilizing	0.983	D	0.426	neutral	None	None	None	None	N
V/Y	0.4759	ambiguous	0.3834	ambiguous	-0.421	Destabilizing	0.836	D	0.457	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.