TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34445	103558;103559;103560	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
N2AB	32804	98635;98636;98637	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
N2A	31877	95854;95855;95856	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
N2B	25380	76363;76364;76365	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
Novex-1	25505	76738;76739;76740	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
Novex-2	25572	76939;76940;76941	chr2:178533282;178533281;178533280	chr2:179398009;179398008;179398007
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-162
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1585
• 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
T/I	rs778587344	-0.336	0.062	N	0.435	0.226	0.284539287134	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.88E-06	0
T/I	rs778587344	-0.336	0.062	N	0.435	0.226	0.284539287134	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	4.77555E-04
T/I	rs778587344	-0.336	0.062	N	0.435	0.226	0.284539287134	gnomAD-4.0.0	3.04481E-06	None	None	None	None	I	None	0	6.14931E-05	None	0	0	None	0	0	1.20492E-06	0	3.40229E-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
T/A	0.1206	likely_benign	0.0882	benign	-1.035	Destabilizing	0.001	N	0.098	neutral	N	0.370419939	None	None	I
T/C	0.7005	likely_pathogenic	0.5702	pathogenic	-0.564	Destabilizing	0.824	D	0.463	neutral	None	None	None	None	I
T/D	0.9133	likely_pathogenic	0.8949	pathogenic	0.335	Stabilizing	0.081	N	0.443	neutral	None	None	None	None	I
T/E	0.9008	likely_pathogenic	0.8877	pathogenic	0.318	Stabilizing	0.081	N	0.433	neutral	None	None	None	None	I
T/F	0.796	likely_pathogenic	0.7348	pathogenic	-1.327	Destabilizing	0.555	D	0.574	neutral	None	None	None	None	I
T/G	0.6498	likely_pathogenic	0.568	pathogenic	-1.241	Destabilizing	0.035	N	0.495	neutral	None	None	None	None	I
T/H	0.8169	likely_pathogenic	0.7865	pathogenic	-1.501	Destabilizing	0.824	D	0.542	neutral	None	None	None	None	I
T/I	0.5934	likely_pathogenic	0.4845	ambiguous	-0.583	Destabilizing	0.062	N	0.435	neutral	N	0.452019815	None	None	I
T/K	0.8814	likely_pathogenic	0.8687	pathogenic	-0.475	Destabilizing	0.081	N	0.459	neutral	None	None	None	None	I
T/L	0.4517	ambiguous	0.367	ambiguous	-0.583	Destabilizing	0.035	N	0.415	neutral	None	None	None	None	I
T/M	0.3367	likely_benign	0.2589	benign	-0.27	Destabilizing	0.555	D	0.471	neutral	None	None	None	None	I
T/N	0.5119	ambiguous	0.4569	ambiguous	-0.356	Destabilizing	0.062	N	0.443	neutral	N	0.508334458	None	None	I
T/P	0.8924	likely_pathogenic	0.8852	pathogenic	-0.704	Destabilizing	0.317	N	0.455	neutral	N	0.484073395	None	None	I
T/Q	0.7758	likely_pathogenic	0.7481	pathogenic	-0.538	Destabilizing	0.38	N	0.475	neutral	None	None	None	None	I
T/R	0.8283	likely_pathogenic	0.8017	pathogenic	-0.285	Destabilizing	0.38	N	0.459	neutral	None	None	None	None	I
T/S	0.1906	likely_benign	0.1814	benign	-0.747	Destabilizing	None	N	0.17	neutral	N	0.467506556	None	None	I
T/V	0.3542	ambiguous	0.2551	benign	-0.704	Destabilizing	0.002	N	0.161	neutral	None	None	None	None	I
T/W	0.971	likely_pathogenic	0.9665	pathogenic	-1.188	Destabilizing	0.935	D	0.592	neutral	None	None	None	None	I
T/Y	0.8554	likely_pathogenic	0.8236	pathogenic	-0.956	Destabilizing	0.555	D	0.565	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.