TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26938	81037;81038;81039	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
N2AB	25297	76114;76115;76116	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
N2A	24370	73333;73334;73335	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
N2B	17873	53842;53843;53844	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
Novex-1	17998	54217;54218;54219	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
Novex-2	18065	54418;54419;54420	chr2:178565320;178565319;178565318	chr2:179430047;179430046;179430045
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-139
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2909
• 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
H/P	None	None	0.917	D	0.533	0.384	0.380052290102	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
H/Q	rs1173826868	-0.499	0.642	N	0.397	0.197	0.206339911435	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
H/Q	rs1173826868	-0.499	0.642	N	0.397	0.197	0.206339911435	gnomAD-4.0.0	6.84268E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99548E-07	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
H/A	0.272	likely_benign	0.2531	benign	-1.384	Destabilizing	0.3	N	0.374	neutral	None	None	None	None	N
H/C	0.1285	likely_benign	0.1207	benign	-0.635	Destabilizing	0.007	N	0.387	neutral	None	None	None	None	N
H/D	0.3231	likely_benign	0.2916	benign	-1.261	Destabilizing	0.784	D	0.491	neutral	N	0.464794325	None	None	N
H/E	0.3289	likely_benign	0.295	benign	-1.117	Destabilizing	0.495	N	0.332	neutral	None	None	None	None	N
H/F	0.2303	likely_benign	0.224	benign	0.26	Stabilizing	0.007	N	0.231	neutral	None	None	None	None	N
H/G	0.356	ambiguous	0.3193	benign	-1.758	Destabilizing	0.665	D	0.418	neutral	None	None	None	None	N
H/I	0.1784	likely_benign	0.1701	benign	-0.306	Destabilizing	0.329	N	0.429	neutral	None	None	None	None	N
H/K	0.2157	likely_benign	0.2057	benign	-1.242	Destabilizing	0.013	N	0.232	neutral	None	None	None	None	N
H/L	0.1015	likely_benign	0.0935	benign	-0.306	Destabilizing	0.139	N	0.39	neutral	N	0.42002204	None	None	N
H/M	0.3343	likely_benign	0.3201	benign	-0.499	Destabilizing	0.944	D	0.493	neutral	None	None	None	None	N
H/N	0.1015	likely_benign	0.1003	benign	-1.455	Destabilizing	0.784	D	0.363	neutral	N	0.443514975	None	None	N
H/P	0.7943	likely_pathogenic	0.7296	pathogenic	-0.651	Destabilizing	0.917	D	0.533	neutral	D	0.527093577	None	None	N
H/Q	0.1508	likely_benign	0.1418	benign	-1.075	Destabilizing	0.642	D	0.397	neutral	N	0.404823301	None	None	N
H/R	0.0984	likely_benign	0.0939	benign	-1.699	Destabilizing	0.473	N	0.367	neutral	N	0.404551155	None	None	N
H/S	0.1884	likely_benign	0.1747	benign	-1.494	Destabilizing	0.329	N	0.411	neutral	None	None	None	None	N
H/T	0.173	likely_benign	0.1637	benign	-1.254	Destabilizing	0.013	N	0.318	neutral	None	None	None	None	N
H/V	0.1561	likely_benign	0.1507	benign	-0.651	Destabilizing	0.013	N	0.41	neutral	None	None	None	None	N
H/W	0.297	likely_benign	0.2811	benign	0.589	Stabilizing	0.981	D	0.486	neutral	None	None	None	None	N
H/Y	0.0925	likely_benign	0.0897	benign	0.537	Stabilizing	0.01	N	0.163	neutral	N	0.432105903	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.