TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6002	18229;18230;18231	chr2:178730529;178730528;178730527	chr2:179595256;179595255;179595254
N2AB	5685	17278;17279;17280	chr2:178730529;178730528;178730527	chr2:179595256;179595255;179595254
N2A	4758	14497;14498;14499	chr2:178730529;178730528;178730527	chr2:179595256;179595255;179595254
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: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-43
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0771
• 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
C/F	rs1415040904	None	0.997	N	0.768	0.409	0.836788012211	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
C/F	rs1415040904	None	0.997	N	0.768	0.409	0.836788012211	gnomAD-4.0.0	1.86158E-06	None	None	None	None	N	None	2.67101E-05	0	None	0	0	None	0	0	0	0	1.60416E-05
C/Y	None	None	0.994	N	0.777	0.432	0.806131679925	gnomAD-4.0.0	6.85234E-07	None	None	None	None	N	None	0	0	None	0	2.52385E-05	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
C/A	0.7083	likely_pathogenic	0.6531	pathogenic	-1.758	Destabilizing	0.982	D	0.641	neutral	None	None	None	None	N
C/D	0.947	likely_pathogenic	0.9397	pathogenic	-0.473	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
C/E	0.9856	likely_pathogenic	0.9858	pathogenic	-0.365	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	N
C/F	0.7524	likely_pathogenic	0.75	pathogenic	-1.139	Destabilizing	0.997	D	0.768	deleterious	N	0.498797062	None	None	N
C/G	0.5291	ambiguous	0.4733	ambiguous	-2.068	Highly Destabilizing	0.997	D	0.794	deleterious	N	0.493365785	None	None	N
C/H	0.9491	likely_pathogenic	0.9424	pathogenic	-2.083	Highly Destabilizing	0.323	N	0.649	neutral	None	None	None	None	N
C/I	0.8726	likely_pathogenic	0.8688	pathogenic	-0.961	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
C/K	0.994	likely_pathogenic	0.9943	pathogenic	-0.953	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
C/L	0.8716	likely_pathogenic	0.8658	pathogenic	-0.961	Destabilizing	0.993	D	0.682	prob.neutral	None	None	None	None	N
C/M	0.8862	likely_pathogenic	0.881	pathogenic	-0.112	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
C/N	0.892	likely_pathogenic	0.8647	pathogenic	-0.943	Destabilizing	0.996	D	0.811	deleterious	None	None	None	None	N
C/P	0.9983	likely_pathogenic	0.9984	pathogenic	-1.201	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
C/Q	0.9682	likely_pathogenic	0.9639	pathogenic	-0.867	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
C/R	0.9646	likely_pathogenic	0.9649	pathogenic	-0.846	Destabilizing	0.997	D	0.819	deleterious	N	0.488326129	None	None	N
C/S	0.5125	ambiguous	0.3905	ambiguous	-1.497	Destabilizing	0.99	D	0.737	prob.delet.	N	0.498424109	None	None	N
C/T	0.5689	likely_pathogenic	0.5088	ambiguous	-1.207	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
C/V	0.7352	likely_pathogenic	0.7248	pathogenic	-1.201	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
C/W	0.9525	likely_pathogenic	0.9466	pathogenic	-1.139	Destabilizing	1.0	D	0.758	deleterious	N	0.491822076	None	None	N
C/Y	0.8886	likely_pathogenic	0.883	pathogenic	-1.107	Destabilizing	0.994	D	0.777	deleterious	N	0.500860977	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.