TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27425	82498;82499;82500	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
N2AB	25784	77575;77576;77577	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
N2A	24857	74794;74795;74796	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
N2B	18360	55303;55304;55305	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
Novex-1	18485	55678;55679;55680	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
Novex-2	18552	55879;55880;55881	chr2:178563859;178563858;178563857	chr2:179428586;179428585;179428584
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-87
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.7985
• 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
Q/R	rs1302788050	0.387	0.211	N	0.459	0.17	0.130388298395	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
Q/R	rs1302788050	0.387	0.211	N	0.459	0.17	0.130388298395	gnomAD-4.0.0	6.36547E-06	None	None	None	None	N	None	0	9.14578E-05	None	0	0	None	0	0	0	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
Q/A	0.146	likely_benign	0.1582	benign	-0.111	Destabilizing	0.035	N	0.411	neutral	None	None	None	None	N
Q/C	0.569	likely_pathogenic	0.6148	pathogenic	0.026	Stabilizing	0.935	D	0.416	neutral	None	None	None	None	N
Q/D	0.3303	likely_benign	0.3598	ambiguous	0.038	Stabilizing	0.149	N	0.445	neutral	None	None	None	None	N
Q/E	0.0796	likely_benign	0.0825	benign	0.011	Stabilizing	0.052	N	0.393	neutral	N	0.40962054	None	None	N
Q/F	0.6124	likely_pathogenic	0.6481	pathogenic	-0.338	Destabilizing	0.555	D	0.414	neutral	None	None	None	None	N
Q/G	0.2223	likely_benign	0.2476	benign	-0.285	Destabilizing	0.149	N	0.437	neutral	None	None	None	None	N
Q/H	0.196	likely_benign	0.2156	benign	-0.08	Destabilizing	0.741	D	0.445	neutral	N	0.470919715	None	None	N
Q/I	0.3013	likely_benign	0.3115	benign	0.256	Stabilizing	0.081	N	0.397	neutral	None	None	None	None	N
Q/K	0.0789	likely_benign	0.0827	benign	0.047	Stabilizing	0.117	N	0.438	neutral	N	0.392266931	None	None	N
Q/L	0.1106	likely_benign	0.1174	benign	0.256	Stabilizing	0.062	N	0.415	neutral	N	0.501242622	None	None	N
Q/M	0.2811	likely_benign	0.2791	benign	0.277	Stabilizing	0.555	D	0.457	neutral	None	None	None	None	N
Q/N	0.2566	likely_benign	0.2733	benign	-0.326	Destabilizing	0.555	D	0.435	neutral	None	None	None	None	N
Q/P	0.0865	likely_benign	0.093	benign	0.161	Stabilizing	None	N	0.207	neutral	N	0.418066665	None	None	N
Q/R	0.0967	likely_benign	0.1008	benign	0.222	Stabilizing	0.211	N	0.459	neutral	N	0.428361017	None	None	N
Q/S	0.1968	likely_benign	0.2044	benign	-0.296	Destabilizing	0.149	N	0.422	neutral	None	None	None	None	N
Q/T	0.1437	likely_benign	0.1474	benign	-0.172	Destabilizing	0.149	N	0.43	neutral	None	None	None	None	N
Q/V	0.1817	likely_benign	0.1901	benign	0.161	Stabilizing	0.002	N	0.261	neutral	None	None	None	None	N
Q/W	0.4813	ambiguous	0.542	ambiguous	-0.359	Destabilizing	0.935	D	0.491	neutral	None	None	None	None	N
Q/Y	0.4223	ambiguous	0.4582	ambiguous	-0.084	Destabilizing	0.791	D	0.447	neutral	None	None	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.