TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25875	77848;77849;77850	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
N2AB	24234	72925;72926;72927	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
N2A	23307	70144;70145;70146	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
N2B	16810	50653;50654;50655	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
Novex-1	16935	51028;51029;51030	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
Novex-2	17002	51229;51230;51231	chr2:178568509;178568508;178568507	chr2:179433236;179433235;179433234
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-136
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.6947
• 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	rs370374073	-0.145	0.003	N	0.101	0.085	None	gnomAD-2.1.1	3.94E-05	None	None	None	None	I	None	4.54846E-04	0	None	0	0	None	0	None	0	0	0
V/A	rs370374073	-0.145	0.003	N	0.101	0.085	None	gnomAD-3.1.2	9.21E-05	None	None	None	None	I	None	2.89603E-04	1.31148E-04	0	0	0	None	0	0	0	0	0
V/A	rs370374073	-0.145	0.003	N	0.101	0.085	None	gnomAD-4.0.0	1.67358E-05	None	None	None	None	I	None	2.93772E-04	3.336E-05	None	0	0	None	0	0	1.69553E-06	0	1.60174E-05
V/I	rs763284241	-0.061	0.007	N	0.249	0.153	0.364926071151	gnomAD-2.1.1	2.82E-05	None	None	None	None	I	None	0	1.45062E-04	None	0	0	None	0	None	0	1.78E-05	0
V/I	rs763284241	-0.061	0.007	N	0.249	0.153	0.364926071151	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs763284241	-0.061	0.007	N	0.249	0.153	0.364926071151	gnomAD-4.0.0	5.57852E-06	None	None	None	None	I	None	1.33526E-05	8.33834E-05	None	0	0	None	0	0	2.5433E-06	0	0
V/L	rs763284241	-0.047	0.309	N	0.35	0.118	0.4722639086	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
V/L	rs763284241	-0.047	0.309	N	0.35	0.118	0.4722639086	gnomAD-4.0.0	6.84346E-07	None	None	None	None	I	None	0	0	None	0	2.5227E-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
V/A	0.0914	likely_benign	0.0857	benign	-0.412	Destabilizing	0.003	N	0.101	neutral	N	0.415365582	None	None	I
V/C	0.5724	likely_pathogenic	0.518	ambiguous	-0.872	Destabilizing	0.987	D	0.355	neutral	None	None	None	None	I
V/D	0.2831	likely_benign	0.2495	benign	-0.377	Destabilizing	0.684	D	0.387	neutral	N	0.455924125	None	None	I
V/E	0.2831	likely_benign	0.2466	benign	-0.488	Destabilizing	0.742	D	0.393	neutral	None	None	None	None	I
V/F	0.1704	likely_benign	0.1406	benign	-0.717	Destabilizing	0.884	D	0.353	neutral	N	0.512990916	None	None	I
V/G	0.1522	likely_benign	0.15	benign	-0.486	Destabilizing	0.521	D	0.408	neutral	N	0.455116049	None	None	I
V/H	0.3964	ambiguous	0.3421	ambiguous	-0.03	Destabilizing	0.996	D	0.367	neutral	None	None	None	None	I
V/I	0.0699	likely_benign	0.066	benign	-0.357	Destabilizing	0.007	N	0.249	neutral	N	0.476376755	None	None	I
V/K	0.2737	likely_benign	0.2313	benign	-0.484	Destabilizing	0.742	D	0.387	neutral	None	None	None	None	I
V/L	0.1484	likely_benign	0.1209	benign	-0.357	Destabilizing	0.309	N	0.35	neutral	N	0.474683244	None	None	I
V/M	0.105	likely_benign	0.0938	benign	-0.609	Destabilizing	0.91	D	0.317	neutral	None	None	None	None	I
V/N	0.1685	likely_benign	0.1396	benign	-0.331	Destabilizing	0.91	D	0.385	neutral	None	None	None	None	I
V/P	0.3381	likely_benign	0.2809	benign	-0.347	Destabilizing	0.009	N	0.313	neutral	None	None	None	None	I
V/Q	0.259	likely_benign	0.2347	benign	-0.532	Destabilizing	0.953	D	0.396	neutral	None	None	None	None	I
V/R	0.2571	likely_benign	0.2124	benign	-0.011	Destabilizing	0.953	D	0.391	neutral	None	None	None	None	I
V/S	0.1179	likely_benign	0.1088	benign	-0.646	Destabilizing	0.101	N	0.269	neutral	None	None	None	None	I
V/T	0.1043	likely_benign	0.092	benign	-0.662	Destabilizing	0.373	N	0.323	neutral	None	None	None	None	I
V/W	0.7378	likely_pathogenic	0.6773	pathogenic	-0.776	Destabilizing	0.996	D	0.477	neutral	None	None	None	None	I
V/Y	0.4528	ambiguous	0.3931	ambiguous	-0.51	Destabilizing	0.984	D	0.353	neutral	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.