TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9745	29458;29459;29460	chr2:178706641;178706640;178706639	chr2:179571368;179571367;179571366
N2AB	9428	28507;28508;28509	chr2:178706641;178706640;178706639	chr2:179571368;179571367;179571366
N2A	8501	25726;25727;25728	chr2:178706641;178706640;178706639	chr2:179571368;179571367;179571366
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-83
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.1482
• 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/I	rs879159098	None	None	None	0.147	0.14	0.167679373172	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	2.23604E-05	None	0	0	None	0	0	8.99426E-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
V/A	0.853	likely_pathogenic	0.694	pathogenic	-1.656	Destabilizing	0.024	N	0.389	neutral	None	None	None	None	N
V/C	0.9103	likely_pathogenic	0.8416	pathogenic	-1.165	Destabilizing	0.628	D	0.559	neutral	None	None	None	None	N
V/D	0.984	likely_pathogenic	0.9392	pathogenic	-1.729	Destabilizing	0.295	N	0.609	neutral	None	None	None	None	N
V/E	0.9701	likely_pathogenic	0.9091	pathogenic	-1.547	Destabilizing	0.356	N	0.59	neutral	None	None	None	None	N
V/F	0.4838	ambiguous	0.2535	benign	-0.887	Destabilizing	0.055	N	0.538	neutral	None	None	None	None	N
V/G	0.8804	likely_pathogenic	0.7153	pathogenic	-2.162	Highly Destabilizing	0.106	N	0.59	neutral	None	None	None	None	N
V/H	0.964	likely_pathogenic	0.9038	pathogenic	-1.889	Destabilizing	0.864	D	0.59	neutral	None	None	None	None	N
V/I	0.0579	likely_benign	0.0551	benign	-0.279	Destabilizing	None	N	0.147	neutral	None	None	None	None	N
V/K	0.9593	likely_pathogenic	0.888	pathogenic	-1.388	Destabilizing	0.136	N	0.585	neutral	None	None	None	None	N
V/L	0.2708	likely_benign	0.1742	benign	-0.279	Destabilizing	None	N	0.15	neutral	None	None	None	None	N
V/M	0.4123	ambiguous	0.251	benign	-0.324	Destabilizing	0.214	N	0.58	neutral	None	None	None	None	N
V/N	0.8906	likely_pathogenic	0.7308	pathogenic	-1.55	Destabilizing	0.628	D	0.611	neutral	None	None	None	None	N
V/P	0.9749	likely_pathogenic	0.9312	pathogenic	-0.706	Destabilizing	0.628	D	0.567	neutral	None	None	None	None	N
V/Q	0.9518	likely_pathogenic	0.8676	pathogenic	-1.419	Destabilizing	0.628	D	0.58	neutral	None	None	None	None	N
V/R	0.9344	likely_pathogenic	0.824	pathogenic	-1.244	Destabilizing	0.356	N	0.609	neutral	None	None	None	None	N
V/S	0.8832	likely_pathogenic	0.7253	pathogenic	-2.204	Highly Destabilizing	0.136	N	0.542	neutral	None	None	None	None	N
V/T	0.8005	likely_pathogenic	0.6735	pathogenic	-1.878	Destabilizing	0.072	N	0.462	neutral	None	None	None	None	N
V/W	0.9666	likely_pathogenic	0.8931	pathogenic	-1.348	Destabilizing	0.864	D	0.609	neutral	None	None	None	None	N
V/Y	0.862	likely_pathogenic	0.693	pathogenic	-0.935	Destabilizing	0.356	N	0.589	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.