TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8284	25075;25076;25077	chr2:178718156;178718155;178718154	chr2:179582883;179582882;179582881
N2AB	7967	24124;24125;24126	chr2:178718156;178718155;178718154	chr2:179582883;179582882;179582881
N2A	7040	21343;21344;21345	chr2:178718156;178718155;178718154	chr2:179582883;179582882;179582881
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: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-68
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4974
• 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/E	None	None	0.001	N	0.229	0.164	0.188950314367	gnomAD-4.0.0	2.40066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-06	0	0
Q/L	None	None	0.269	N	0.514	0.209	0.442054744378	gnomAD-4.0.0	3.21576E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71948E-06	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	0.29	likely_benign	0.2994	benign	-0.629	Destabilizing	0.336	N	0.427	neutral	None	None	None	None	N
Q/C	0.662	likely_pathogenic	0.6195	pathogenic	-0.018	Destabilizing	0.968	D	0.55	neutral	None	None	None	None	N
Q/D	0.5105	ambiguous	0.5528	ambiguous	-0.385	Destabilizing	0.071	N	0.409	neutral	None	None	None	None	N
Q/E	0.106	likely_benign	0.1042	benign	-0.299	Destabilizing	0.001	N	0.229	neutral	N	0.391219286	None	None	N
Q/F	0.6508	likely_pathogenic	0.6024	pathogenic	-0.34	Destabilizing	0.937	D	0.556	neutral	None	None	None	None	N
Q/G	0.4178	ambiguous	0.4235	ambiguous	-0.975	Destabilizing	0.551	D	0.506	neutral	None	None	None	None	N
Q/H	0.2027	likely_benign	0.1963	benign	-0.751	Destabilizing	0.724	D	0.494	neutral	N	0.474974033	None	None	N
Q/I	0.3472	ambiguous	0.3147	benign	0.248	Stabilizing	0.776	D	0.568	neutral	None	None	None	None	N
Q/K	0.0997	likely_benign	0.0953	benign	-0.283	Destabilizing	None	N	0.257	neutral	N	0.457444278	None	None	N
Q/L	0.1494	likely_benign	0.1359	benign	0.248	Stabilizing	0.269	N	0.514	neutral	N	0.499947048	None	None	N
Q/M	0.4034	ambiguous	0.3545	ambiguous	0.598	Stabilizing	0.914	D	0.499	neutral	None	None	None	None	N
Q/N	0.3567	ambiguous	0.3651	ambiguous	-0.831	Destabilizing	0.269	N	0.408	neutral	None	None	None	None	N
Q/P	0.5327	ambiguous	0.6342	pathogenic	-0.013	Destabilizing	0.36	N	0.529	neutral	N	0.481534646	None	None	N
Q/R	0.1046	likely_benign	0.0966	benign	-0.197	Destabilizing	0.001	N	0.214	neutral	N	0.464679681	None	None	N
Q/S	0.2777	likely_benign	0.2763	benign	-0.915	Destabilizing	0.336	N	0.407	neutral	None	None	None	None	N
Q/T	0.1901	likely_benign	0.175	benign	-0.631	Destabilizing	0.045	N	0.467	neutral	None	None	None	None	N
Q/V	0.2452	likely_benign	0.2236	benign	-0.013	Destabilizing	0.128	N	0.518	neutral	None	None	None	None	N
Q/W	0.5178	ambiguous	0.4689	ambiguous	-0.203	Destabilizing	0.993	D	0.577	neutral	None	None	None	None	N
Q/Y	0.4431	ambiguous	0.423	ambiguous	0.01	Stabilizing	0.937	D	0.555	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.