TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27736	83431;83432;83433	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
N2AB	26095	78508;78509;78510	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
N2A	25168	75727;75728;75729	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
N2B	18671	56236;56237;56238	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
Novex-1	18796	56611;56612;56613	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
Novex-2	18863	56812;56813;56814	chr2:178562926;178562925;178562924	chr2:179427653;179427652;179427651
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-141
• Domain position: 61
• Structural Position: 144
• Q(SASA): 0.1049
• 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/A	rs1370518448	None	0.63	N	0.526	0.362	0.698509492642	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs1370518448	None	0.63	N	0.526	0.362	0.698509492642	gnomAD-4.0.0	2.56282E-06	None	None	None	None	N	None	0	0	None	4.09065E-05	0	None	0	0	2.39335E-06	0	0
V/F	rs373638788	-1.609	0.983	D	0.72	0.691	0.839994840878	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/F	rs373638788	-1.609	0.983	D	0.72	0.691	0.839994840878	gnomAD-4.0.0	2.73718E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59801E-06	0	0
V/I	rs373638788	-0.849	0.873	N	0.53	0.362	0.614010665196	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
V/I	rs373638788	-0.849	0.873	N	0.53	0.362	0.614010665196	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs373638788	-0.849	0.873	N	0.53	0.362	0.614010665196	gnomAD-4.0.0	6.19775E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.47634E-06	0	0
V/L	None	None	0.773	N	0.537	0.479	0.727553539088	gnomAD-4.0.0	1.36859E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31873E-05	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	0.5539	ambiguous	0.5646	pathogenic	-1.834	Destabilizing	0.63	D	0.526	neutral	N	0.500005763	None	None	N
V/C	0.8833	likely_pathogenic	0.8862	pathogenic	-2.369	Highly Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
V/D	0.9937	likely_pathogenic	0.9944	pathogenic	-3.245	Highly Destabilizing	0.967	D	0.739	prob.delet.	D	0.556007706	None	None	N
V/E	0.9885	likely_pathogenic	0.9899	pathogenic	-3.157	Highly Destabilizing	0.975	D	0.693	prob.neutral	None	None	None	None	N
V/F	0.9612	likely_pathogenic	0.9675	pathogenic	-1.401	Destabilizing	0.983	D	0.72	prob.delet.	D	0.543890932	None	None	N
V/G	0.8601	likely_pathogenic	0.8732	pathogenic	-2.189	Highly Destabilizing	0.805	D	0.689	prob.neutral	D	0.544397911	None	None	N
V/H	0.9968	likely_pathogenic	0.9971	pathogenic	-1.606	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
V/I	0.1776	likely_benign	0.1969	benign	-0.9	Destabilizing	0.873	D	0.53	neutral	N	0.493369466	None	None	N
V/K	0.9926	likely_pathogenic	0.9934	pathogenic	-1.728	Destabilizing	0.975	D	0.697	prob.neutral	None	None	None	None	N
V/L	0.7962	likely_pathogenic	0.8254	pathogenic	-0.9	Destabilizing	0.773	D	0.537	neutral	N	0.506135031	None	None	N
V/M	0.7137	likely_pathogenic	0.7704	pathogenic	-1.223	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
V/N	0.9652	likely_pathogenic	0.9699	pathogenic	-2.046	Highly Destabilizing	0.975	D	0.748	deleterious	None	None	None	None	N
V/P	0.9807	likely_pathogenic	0.9826	pathogenic	-1.184	Destabilizing	0.987	D	0.717	prob.delet.	None	None	None	None	N
V/Q	0.9858	likely_pathogenic	0.9877	pathogenic	-2.176	Highly Destabilizing	0.975	D	0.715	prob.delet.	None	None	None	None	N
V/R	0.9888	likely_pathogenic	0.989	pathogenic	-1.255	Destabilizing	0.975	D	0.748	deleterious	None	None	None	None	N
V/S	0.7862	likely_pathogenic	0.8029	pathogenic	-2.487	Highly Destabilizing	0.253	N	0.471	neutral	None	None	None	None	N
V/T	0.5922	likely_pathogenic	0.6161	pathogenic	-2.286	Highly Destabilizing	0.845	D	0.547	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9996	pathogenic	-1.7	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
V/Y	0.996	likely_pathogenic	0.9965	pathogenic	-1.367	Destabilizing	0.996	D	0.721	prob.delet.	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.