TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6749	20470;20471;20472	chr2:178727120;178727119;178727118	chr2:179591847;179591846;179591845
N2AB	6432	19519;19520;19521	chr2:178727120;178727119;178727118	chr2:179591847;179591846;179591845
N2A	5505	16738;16739;16740	chr2:178727120;178727119;178727118	chr2:179591847;179591846;179591845
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-51
• Domain position: 83
• Structural Position: 166
• Q(SASA): 0.1612
• 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/R	rs2079475430	None	0.029	N	0.529	0.181	0.31411915649	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	3.16456E-03	0	0	0
T/R	rs2079475430	None	0.029	N	0.529	0.181	0.31411915649	gnomAD-4.0.0	1.88295E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.67224E-04	0	0	3.25024E-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	0.0579	likely_benign	0.0618	benign	-0.996	Destabilizing	None	N	0.092	neutral	N	0.366918274	None	None	I
T/C	0.4683	ambiguous	0.5036	ambiguous	-0.599	Destabilizing	0.356	N	0.513	neutral	None	None	None	None	I
T/D	0.2903	likely_benign	0.3302	benign	0.184	Stabilizing	None	N	0.184	neutral	None	None	None	None	I
T/E	0.3026	likely_benign	0.3624	ambiguous	0.199	Stabilizing	0.016	N	0.439	neutral	None	None	None	None	I
T/F	0.2627	likely_benign	0.2832	benign	-1.117	Destabilizing	0.214	N	0.623	neutral	None	None	None	None	I
T/G	0.2385	likely_benign	0.2589	benign	-1.251	Destabilizing	0.016	N	0.473	neutral	None	None	None	None	I
T/H	0.2806	likely_benign	0.3179	benign	-1.397	Destabilizing	0.628	D	0.587	neutral	None	None	None	None	I
T/I	0.1474	likely_benign	0.1744	benign	-0.403	Destabilizing	None	N	0.217	neutral	N	0.464410322	None	None	I
T/K	0.2599	likely_benign	0.3187	benign	-0.528	Destabilizing	None	N	0.209	neutral	N	0.478915628	None	None	I
T/L	0.1142	likely_benign	0.1205	benign	-0.403	Destabilizing	0.002	N	0.383	neutral	None	None	None	None	I
T/M	0.1021	likely_benign	0.1037	benign	-0.213	Destabilizing	0.214	N	0.517	neutral	None	None	None	None	I
T/N	0.1236	likely_benign	0.1353	benign	-0.508	Destabilizing	0.072	N	0.361	neutral	None	None	None	None	I
T/P	0.5946	likely_pathogenic	0.6605	pathogenic	-0.569	Destabilizing	0.106	N	0.516	neutral	D	0.523842628	None	None	I
T/Q	0.2479	likely_benign	0.2889	benign	-0.62	Destabilizing	0.072	N	0.564	neutral	None	None	None	None	I
T/R	0.1989	likely_benign	0.2419	benign	-0.337	Destabilizing	0.029	N	0.529	neutral	N	0.490652774	None	None	I
T/S	0.0908	likely_benign	0.0955	benign	-0.891	Destabilizing	0.012	N	0.353	neutral	N	0.455654766	None	None	I
T/V	0.1132	likely_benign	0.1267	benign	-0.569	Destabilizing	None	N	0.12	neutral	None	None	None	None	I
T/W	0.7085	likely_pathogenic	0.7371	pathogenic	-1.004	Destabilizing	0.864	D	0.574	neutral	None	None	None	None	I
T/Y	0.3195	likely_benign	0.3498	ambiguous	-0.766	Destabilizing	0.356	N	0.615	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.