TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33497	100714;100715;100716	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
N2AB	31856	95791;95792;95793	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
N2A	30929	93010;93011;93012	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
N2B	24432	73519;73520;73521	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
Novex-1	24557	73894;73895;73896	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
Novex-2	24624	74095;74096;74097	chr2:178536258;178536257;178536256	chr2:179400985;179400984;179400983
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-158
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4582
• 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
H/Q	rs746874226	-0.162	0.005	N	0.167	0.137	0.250579442822	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	9.95E-05	0	None	0	None	0	0	0
H/Q	rs746874226	-0.162	0.005	N	0.167	0.137	0.250579442822	gnomAD-4.0.0	6.84331E-07	None	None	None	None	I	None	0	0	None	3.82848E-05	0	None	0	0	0	0	0
H/Y	rs768361337	1.307	0.758	N	0.224	0.224	0.293147016451	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.82E-05	None	0	0	0
H/Y	rs768361337	1.307	0.758	N	0.224	0.224	0.293147016451	gnomAD-4.0.0	1.27351E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.14669E-04	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
H/A	0.1695	likely_benign	0.1682	benign	-0.423	Destabilizing	0.002	N	0.175	neutral	None	None	None	None	I
H/C	0.135	likely_benign	0.1294	benign	0.043	Stabilizing	0.887	D	0.304	neutral	None	None	None	None	I
H/D	0.2503	likely_benign	0.285	benign	-0.475	Destabilizing	0.215	N	0.306	neutral	N	0.428622881	None	None	I
H/E	0.2459	likely_benign	0.3005	benign	-0.386	Destabilizing	0.094	N	0.167	neutral	None	None	None	None	I
H/F	0.2374	likely_benign	0.2186	benign	0.775	Stabilizing	0.401	N	0.369	neutral	None	None	None	None	I
H/G	0.2903	likely_benign	0.2892	benign	-0.766	Destabilizing	0.199	N	0.228	neutral	None	None	None	None	I
H/I	0.1527	likely_benign	0.1678	benign	0.511	Stabilizing	0.09	N	0.283	neutral	None	None	None	None	I
H/K	0.174	likely_benign	0.2157	benign	-0.316	Destabilizing	0.09	N	0.235	neutral	None	None	None	None	I
H/L	0.0931	likely_benign	0.0941	benign	0.511	Stabilizing	0.032	N	0.245	neutral	N	0.43048975	None	None	I
H/M	0.3254	likely_benign	0.322	benign	0.188	Stabilizing	0.018	N	0.206	neutral	None	None	None	None	I
H/N	0.0883	likely_benign	0.0919	benign	-0.63	Destabilizing	0.215	N	0.199	neutral	N	0.441186746	None	None	I
H/P	0.7102	likely_pathogenic	0.7283	pathogenic	0.222	Stabilizing	0.356	N	0.393	neutral	N	0.493962438	None	None	I
H/Q	0.1133	likely_benign	0.1257	benign	-0.414	Destabilizing	0.005	N	0.167	neutral	N	0.420656758	None	None	I
H/R	0.0878	likely_benign	0.1027	benign	-0.817	Destabilizing	0.153	N	0.186	neutral	N	0.400185486	None	None	I
H/S	0.1445	likely_benign	0.1484	benign	-0.613	Destabilizing	0.199	N	0.228	neutral	None	None	None	None	I
H/T	0.1443	likely_benign	0.1615	benign	-0.405	Destabilizing	0.13	N	0.245	neutral	None	None	None	None	I
H/V	0.1217	likely_benign	0.1342	benign	0.222	Stabilizing	0.001	N	0.221	neutral	None	None	None	None	I
H/W	0.4254	ambiguous	0.4286	ambiguous	1.032	Stabilizing	0.993	D	0.305	neutral	None	None	None	None	I
H/Y	0.097	likely_benign	0.0917	benign	1.085	Stabilizing	0.758	D	0.224	neutral	N	0.42806552	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.