TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27688	83287;83288;83289	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
N2AB	26047	78364;78365;78366	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
N2A	25120	75583;75584;75585	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
N2B	18623	56092;56093;56094	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
Novex-1	18748	56467;56468;56469	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
Novex-2	18815	56668;56669;56670	chr2:178563070;178563069;178563068	chr2:179427797;179427796;179427795
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-141
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.7637
• 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
R/C	rs757441189	-0.191	1.0	D	0.696	0.567	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/C	rs757441189	-0.191	1.0	D	0.696	0.567	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	6.32911E-03	0	0	0
R/C	rs757441189	-0.191	1.0	D	0.696	0.567	None	gnomAD-4.0.0	4.77432E-06	None	None	None	None	I	None	5.65739E-05	0	None	0	0	None	0	0	0	1.43271E-05	3.02444E-05
R/H	rs185002960	-0.61	0.999	N	0.606	0.411	None	gnomAD-2.1.1	3.72487E-03	None	None	None	None	I	None	3.3066E-04	1.69635E-04	None	1.93311E-04	3.07535E-04	None	1.96091E-04	None	3.14775E-02	1.62335E-03	2.94613E-03
R/H	rs185002960	-0.61	0.999	N	0.606	0.411	None	gnomAD-3.1.2	3.05147E-03	None	None	None	None	I	None	3.13813E-04	6.57E-05	0	2.88184E-04	0	None	3.23463E-02	0	1.47016E-03	2.07297E-04	2.39234E-03
R/H	rs185002960	-0.61	0.999	N	0.606	0.411	None	1000 genomes	1.39776E-03	None	None	None	None	I	None	0	0	None	None	0	6E-03	None	None	None	1E-03	None
R/H	rs185002960	-0.61	0.999	N	0.606	0.411	None	gnomAD-4.0.0	1.95397E-03	None	None	None	None	I	None	3.3328E-04	1.83425E-04	None	2.02716E-04	3.79041E-04	None	2.99128E-02	0	9.01918E-04	9.88186E-05	1.71271E-03
R/L	None	None	0.975	N	0.59	0.423	0.708922172023	gnomAD-4.0.0	6.84244E-07	None	None	None	None	I	None	2.98829E-05	0	None	0	0	None	0	0	0	0	0
R/P	rs185002960	0.319	0.109	N	0.545	0.39	0.519514513453	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/P	rs185002960	0.319	0.109	N	0.545	0.39	0.519514513453	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
R/P	rs185002960	0.319	0.109	N	0.545	0.39	0.519514513453	gnomAD-4.0.0	4.33802E-06	None	None	None	None	I	None	7.99893E-05	0	None	0	0	None	0	0	0	0	1.60067E-05

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
R/A	0.9502	likely_pathogenic	0.9608	pathogenic	0.036	Stabilizing	0.953	D	0.615	neutral	None	None	None	None	I
R/C	0.6926	likely_pathogenic	0.7576	pathogenic	-0.237	Destabilizing	1.0	D	0.696	prob.neutral	D	0.527727871	None	None	I
R/D	0.9818	likely_pathogenic	0.9846	pathogenic	-0.226	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	I
R/E	0.9157	likely_pathogenic	0.9226	pathogenic	-0.174	Destabilizing	0.953	D	0.639	neutral	None	None	None	None	I
R/F	0.9582	likely_pathogenic	0.9672	pathogenic	-0.244	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
R/G	0.8955	likely_pathogenic	0.9137	pathogenic	-0.125	Destabilizing	0.975	D	0.6	neutral	D	0.537981313	None	None	I
R/H	0.2997	likely_benign	0.3646	ambiguous	-0.599	Destabilizing	0.999	D	0.606	neutral	N	0.515611097	None	None	I
R/I	0.9412	likely_pathogenic	0.9442	pathogenic	0.419	Stabilizing	0.993	D	0.665	neutral	None	None	None	None	I
R/K	0.2591	likely_benign	0.3138	benign	-0.123	Destabilizing	0.893	D	0.57	neutral	None	None	None	None	I
R/L	0.8285	likely_pathogenic	0.8487	pathogenic	0.419	Stabilizing	0.975	D	0.59	neutral	N	0.484073395	None	None	I
R/M	0.8978	likely_pathogenic	0.9108	pathogenic	-0.042	Destabilizing	0.999	D	0.602	neutral	None	None	None	None	I
R/N	0.9628	likely_pathogenic	0.9692	pathogenic	-0.026	Destabilizing	0.993	D	0.608	neutral	None	None	None	None	I
R/P	0.854	likely_pathogenic	0.9	pathogenic	0.31	Stabilizing	0.109	N	0.545	neutral	N	0.506647875	None	None	I
R/Q	0.368	ambiguous	0.4221	ambiguous	-0.075	Destabilizing	0.993	D	0.613	neutral	None	None	None	None	I
R/S	0.9682	likely_pathogenic	0.9745	pathogenic	-0.26	Destabilizing	0.975	D	0.603	neutral	N	0.49797046	None	None	I
R/T	0.931	likely_pathogenic	0.9398	pathogenic	-0.09	Destabilizing	0.953	D	0.598	neutral	None	None	None	None	I
R/V	0.9453	likely_pathogenic	0.9476	pathogenic	0.31	Stabilizing	0.993	D	0.661	neutral	None	None	None	None	I
R/W	0.6647	likely_pathogenic	0.7135	pathogenic	-0.387	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
R/Y	0.8751	likely_pathogenic	0.9009	pathogenic	0.027	Stabilizing	0.998	D	0.655	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.