TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16981	51166;51167;51168	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
N2AB	15340	46243;46244;46245	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
N2A	14413	43462;43463;43464	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
N2B	7916	23971;23972;23973	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
Novex-1	8041	24346;24347;24348	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
Novex-2	8108	24547;24548;24549	chr2:178611188;178611187;178611186	chr2:179475915;179475914;179475913
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-111
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6235
• 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/A	rs1323997384	None	0.999	N	0.577	0.351	0.651059218688	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs1323997384	None	0.999	N	0.577	0.351	0.651059218688	gnomAD-4.0.0	6.58025E-06	None	None	None	None	I	None	2.41488E-05	0	None	0	0	None	0	0	0	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	0.4772	ambiguous	0.4298	ambiguous	-0.419	Destabilizing	0.999	D	0.577	neutral	N	0.478166859	None	None	I
V/C	0.8521	likely_pathogenic	0.8451	pathogenic	-0.675	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
V/D	0.8564	likely_pathogenic	0.8057	pathogenic	-0.63	Destabilizing	1.0	D	0.76	deleterious	N	0.484814305	None	None	I
V/E	0.723	likely_pathogenic	0.6625	pathogenic	-0.73	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
V/F	0.28	likely_benign	0.2523	benign	-0.644	Destabilizing	1.0	D	0.742	deleterious	N	0.496167006	None	None	I
V/G	0.6598	likely_pathogenic	0.5808	pathogenic	-0.539	Destabilizing	1.0	D	0.738	prob.delet.	N	0.504439297	None	None	I
V/H	0.8355	likely_pathogenic	0.7983	pathogenic	-0.068	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	I
V/I	0.0932	likely_benign	0.0911	benign	-0.239	Destabilizing	0.997	D	0.493	neutral	N	0.496167006	None	None	I
V/K	0.6927	likely_pathogenic	0.6369	pathogenic	-0.544	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
V/L	0.3507	ambiguous	0.3232	benign	-0.239	Destabilizing	0.997	D	0.574	neutral	N	0.505846909	None	None	I
V/M	0.2575	likely_benign	0.2318	benign	-0.494	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
V/N	0.6371	likely_pathogenic	0.6007	pathogenic	-0.315	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
V/P	0.9507	likely_pathogenic	0.923	pathogenic	-0.267	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
V/Q	0.6356	likely_pathogenic	0.5769	pathogenic	-0.546	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
V/R	0.6032	likely_pathogenic	0.5257	ambiguous	-0.02	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
V/S	0.4891	ambiguous	0.4519	ambiguous	-0.596	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
V/T	0.4523	ambiguous	0.4276	ambiguous	-0.602	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
V/W	0.9321	likely_pathogenic	0.9028	pathogenic	-0.737	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
V/Y	0.757	likely_pathogenic	0.719	pathogenic	-0.447	Destabilizing	1.0	D	0.745	deleterious	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.