TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9787	29584;29585;29586	chr2:178706515;178706514;178706513	chr2:179571242;179571241;179571240
N2AB	9470	28633;28634;28635	chr2:178706515;178706514;178706513	chr2:179571242;179571241;179571240
N2A	8543	25852;25853;25854	chr2:178706515;178706514;178706513	chr2:179571242;179571241;179571240
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-83
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.4656
• 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	None	None	0.642	None	0.185	0.258	0.166414681773	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.4673	ambiguous	0.3911	ambiguous	-0.646	Destabilizing	0.495	N	0.365	neutral	None	None	None	None	N
Q/C	0.9317	likely_pathogenic	0.8597	pathogenic	-0.022	Destabilizing	0.995	D	0.419	neutral	None	None	None	None	N
Q/D	0.788	likely_pathogenic	0.6326	pathogenic	-0.557	Destabilizing	0.003	N	0.093	neutral	None	None	None	None	N
Q/E	0.131	likely_benign	0.1012	benign	-0.494	Destabilizing	0.002	N	0.087	neutral	None	None	None	None	N
Q/F	0.8625	likely_pathogenic	0.7698	pathogenic	-0.44	Destabilizing	0.893	D	0.472	neutral	None	None	None	None	N
Q/G	0.8063	likely_pathogenic	0.6587	pathogenic	-0.972	Destabilizing	0.495	N	0.401	neutral	None	None	None	None	N
Q/H	0.442	ambiguous	0.323	benign	-0.858	Destabilizing	0.002	N	0.092	neutral	None	None	None	None	N
Q/I	0.448	ambiguous	0.3834	ambiguous	0.168	Stabilizing	0.543	D	0.512	neutral	None	None	None	None	N
Q/K	0.2091	likely_benign	0.1532	benign	-0.366	Destabilizing	0.27	N	0.23	neutral	None	None	None	None	N
Q/L	0.2579	likely_benign	0.1934	benign	0.168	Stabilizing	0.006	N	0.209	neutral	None	None	None	None	N
Q/M	0.4761	ambiguous	0.4402	ambiguous	0.659	Stabilizing	0.893	D	0.318	neutral	None	None	None	None	N
Q/N	0.6161	likely_pathogenic	0.4993	ambiguous	-0.871	Destabilizing	0.013	N	0.098	neutral	None	None	None	None	N
Q/P	0.9685	likely_pathogenic	0.866	pathogenic	-0.072	Destabilizing	0.784	D	0.437	neutral	None	None	None	None	N
Q/R	0.2729	likely_benign	0.1775	benign	-0.242	Destabilizing	0.642	D	0.185	neutral	None	None	None	None	N
Q/S	0.5493	ambiguous	0.4783	ambiguous	-0.941	Destabilizing	0.495	N	0.209	neutral	None	None	None	None	N
Q/T	0.332	likely_benign	0.2961	benign	-0.69	Destabilizing	0.495	N	0.349	neutral	None	None	None	None	N
Q/V	0.3265	likely_benign	0.2853	benign	-0.072	Destabilizing	0.543	D	0.418	neutral	None	None	None	None	N
Q/W	0.8639	likely_pathogenic	0.7128	pathogenic	-0.305	Destabilizing	0.995	D	0.411	neutral	None	None	None	None	N
Q/Y	0.7737	likely_pathogenic	0.6155	pathogenic	-0.096	Destabilizing	0.704	D	0.437	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.