TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20925	62998;62999;63000	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
N2AB	19284	58075;58076;58077	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
N2A	18357	55294;55295;55296	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
N2B	11860	35803;35804;35805	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
Novex-1	11985	36178;36179;36180	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
Novex-2	12052	36379;36380;36381	chr2:178588952;178588951;178588950	chr2:179453679;179453678;179453677
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: Fn3-39
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1266
• 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/E	rs755147938	-2.252	0.988	D	0.789	0.632	0.866241633211	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
V/E	rs755147938	-2.252	0.988	D	0.789	0.632	0.866241633211	gnomAD-4.0.0	1.59368E-06	None	None	None	None	N	None	0	2.29116E-05	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	0.6812	likely_pathogenic	0.727	pathogenic	-1.991	Destabilizing	0.826	D	0.681	prob.neutral	D	0.523431622	None	None	N
V/C	0.9387	likely_pathogenic	0.9499	pathogenic	-1.671	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/D	0.9962	likely_pathogenic	0.9966	pathogenic	-2.373	Highly Destabilizing	0.991	D	0.821	deleterious	None	None	None	None	N
V/E	0.9868	likely_pathogenic	0.9885	pathogenic	-2.121	Highly Destabilizing	0.988	D	0.789	deleterious	D	0.537845366	None	None	N
V/F	0.7378	likely_pathogenic	0.7839	pathogenic	-1.205	Destabilizing	0.982	D	0.798	deleterious	None	None	None	None	N
V/G	0.9227	likely_pathogenic	0.9334	pathogenic	-2.577	Highly Destabilizing	0.959	D	0.781	deleterious	D	0.537845366	None	None	N
V/H	0.9939	likely_pathogenic	0.9956	pathogenic	-2.374	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/I	0.0876	likely_benign	0.0951	benign	-0.344	Destabilizing	0.704	D	0.639	neutral	N	0.514577279	None	None	N
V/K	0.9897	likely_pathogenic	0.9918	pathogenic	-1.669	Destabilizing	0.969	D	0.78	deleterious	None	None	None	None	N
V/L	0.5327	ambiguous	0.5797	pathogenic	-0.344	Destabilizing	0.509	D	0.508	neutral	D	0.523231261	None	None	N
V/M	0.5109	ambiguous	0.5792	pathogenic	-0.452	Destabilizing	0.373	N	0.411	neutral	None	None	None	None	N
V/N	0.9817	likely_pathogenic	0.9854	pathogenic	-2.065	Highly Destabilizing	0.991	D	0.821	deleterious	None	None	None	None	N
V/P	0.9817	likely_pathogenic	0.9834	pathogenic	-0.865	Destabilizing	0.997	D	0.804	deleterious	None	None	None	None	N
V/Q	0.9818	likely_pathogenic	0.9853	pathogenic	-1.823	Destabilizing	0.991	D	0.811	deleterious	None	None	None	None	N
V/R	0.9842	likely_pathogenic	0.9868	pathogenic	-1.648	Destabilizing	0.991	D	0.829	deleterious	None	None	None	None	N
V/S	0.9281	likely_pathogenic	0.9408	pathogenic	-2.752	Highly Destabilizing	0.884	D	0.769	deleterious	None	None	None	None	N
V/T	0.8295	likely_pathogenic	0.8607	pathogenic	-2.326	Highly Destabilizing	0.17	N	0.355	neutral	None	None	None	None	N
V/W	0.9957	likely_pathogenic	0.9969	pathogenic	-1.7	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/Y	0.9792	likely_pathogenic	0.9838	pathogenic	-1.29	Destabilizing	0.997	D	0.785	deleterious	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.