TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7449	22570;22571;22572	chr2:178722442;178722441;178722440	chr2:179587169;179587168;179587167
N2AB	7132	21619;21620;21621	chr2:178722442;178722441;178722440	chr2:179587169;179587168;179587167
N2A	6205	18838;18839;18840	chr2:178722442;178722441;178722440	chr2:179587169;179587168;179587167
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-59
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7436
• 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
Q/L	rs1269849836	0.476	0.103	N	0.289	0.289	0.506432333661	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
Q/L	rs1269849836	0.476	0.103	N	0.289	0.289	0.506432333661	gnomAD-4.0.0	1.59197E-06	None	None	None	None	I	None	0	2.28718E-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	0.169	likely_benign	0.175	benign	-0.137	Destabilizing	0.067	N	0.23	neutral	None	None	None	None	I
Q/C	0.5824	likely_pathogenic	0.6244	pathogenic	0.104	Stabilizing	0.924	D	0.403	neutral	None	None	None	None	I
Q/D	0.1815	likely_benign	0.2044	benign	-0.013	Destabilizing	0.048	N	0.171	neutral	None	None	None	None	I
Q/E	0.06	likely_benign	0.0619	benign	-0.04	Destabilizing	None	N	0.077	neutral	N	0.414288146	None	None	I
Q/F	0.5533	ambiguous	0.5614	ambiguous	-0.359	Destabilizing	0.88	D	0.515	neutral	None	None	None	None	I
Q/G	0.2297	likely_benign	0.2412	benign	-0.318	Destabilizing	0.143	N	0.266	neutral	None	None	None	None	I
Q/H	0.1126	likely_benign	0.1294	benign	-0.165	Destabilizing	0.002	N	0.145	neutral	N	0.503968788	None	None	I
Q/I	0.327	likely_benign	0.3429	ambiguous	0.248	Stabilizing	0.425	N	0.503	neutral	None	None	None	None	I
Q/K	0.0822	likely_benign	0.0859	benign	0.057	Stabilizing	0.048	N	0.188	neutral	N	0.479262345	None	None	I
Q/L	0.1293	likely_benign	0.1307	benign	0.248	Stabilizing	0.103	N	0.289	neutral	N	0.481708004	None	None	I
Q/M	0.3341	likely_benign	0.3469	ambiguous	0.358	Stabilizing	0.941	D	0.389	neutral	None	None	None	None	I
Q/N	0.1598	likely_benign	0.1784	benign	-0.268	Destabilizing	0.003	N	0.101	neutral	None	None	None	None	I
Q/P	0.2802	likely_benign	0.3191	benign	0.148	Stabilizing	0.46	N	0.393	neutral	N	0.492013114	None	None	I
Q/R	0.0845	likely_benign	0.089	benign	0.224	Stabilizing	0.131	N	0.303	neutral	N	0.485054953	None	None	I
Q/S	0.147	likely_benign	0.1555	benign	-0.248	Destabilizing	0.01	N	0.099	neutral	None	None	None	None	I
Q/T	0.1262	likely_benign	0.1361	benign	-0.125	Destabilizing	None	N	0.168	neutral	None	None	None	None	I
Q/V	0.2109	likely_benign	0.2158	benign	0.148	Stabilizing	0.044	N	0.313	neutral	None	None	None	None	I
Q/W	0.4145	ambiguous	0.4317	ambiguous	-0.366	Destabilizing	0.996	D	0.406	neutral	None	None	None	None	I
Q/Y	0.3114	likely_benign	0.3325	benign	-0.097	Destabilizing	0.341	N	0.489	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.