TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6886	20881;20882;20883	chr2:178725548;178725547;178725546	chr2:179590275;179590274;179590273
N2AB	6569	19930;19931;19932	chr2:178725548;178725547;178725546	chr2:179590275;179590274;179590273
N2A	5642	17149;17150;17151	chr2:178725548;178725547;178725546	chr2:179590275;179590274;179590273
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-53
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2755
• 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/P	None	None	0.202	D	0.499	0.391	0.318828661733	gnomAD-4.0.0	6.84516E-07	None	None	None	None	N	None	0	0	None	0	2.5208E-05	None	0	0	0	0	0
Q/R	None	None	0.025	N	0.369	0.263	0.132336055621	gnomAD-4.0.0	6.84516E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99734E-07	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	0.2644	likely_benign	0.239	benign	-0.608	Destabilizing	0.015	N	0.304	neutral	None	None	None	None	N
Q/C	0.6324	likely_pathogenic	0.5539	ambiguous	-0.015	Destabilizing	0.781	D	0.543	neutral	None	None	None	None	N
Q/D	0.4498	ambiguous	0.4015	ambiguous	-0.591	Destabilizing	0.033	N	0.317	neutral	None	None	None	None	N
Q/E	0.0845	likely_benign	0.0792	benign	-0.48	Destabilizing	None	N	0.163	neutral	N	0.45344118	None	None	N
Q/F	0.6489	likely_pathogenic	0.5894	pathogenic	-0.175	Destabilizing	0.142	N	0.603	neutral	None	None	None	None	N
Q/G	0.3643	ambiguous	0.3301	benign	-0.983	Destabilizing	0.064	N	0.38	neutral	None	None	None	None	N
Q/H	0.202	likely_benign	0.1682	benign	-0.771	Destabilizing	None	N	0.184	neutral	N	0.487729899	None	None	N
Q/I	0.3361	likely_benign	0.3031	benign	0.357	Stabilizing	0.076	N	0.519	neutral	None	None	None	None	N
Q/K	0.1127	likely_benign	0.1019	benign	-0.505	Destabilizing	0.001	N	0.157	neutral	N	0.45448133	None	None	N
Q/L	0.1324	likely_benign	0.117	benign	0.357	Stabilizing	None	N	0.331	neutral	N	0.452809249	None	None	N
Q/M	0.3549	ambiguous	0.321	benign	0.658	Stabilizing	0.367	N	0.419	neutral	None	None	None	None	N
Q/N	0.3115	likely_benign	0.2731	benign	-1.003	Destabilizing	0.064	N	0.357	neutral	None	None	None	None	N
Q/P	0.7638	likely_pathogenic	0.7311	pathogenic	0.067	Stabilizing	0.202	N	0.499	neutral	D	0.531270033	None	None	N
Q/R	0.1159	likely_benign	0.1086	benign	-0.457	Destabilizing	0.025	N	0.369	neutral	N	0.455348122	None	None	N
Q/S	0.2538	likely_benign	0.2299	benign	-1.08	Destabilizing	0.001	N	0.143	neutral	None	None	None	None	N
Q/T	0.1799	likely_benign	0.1524	benign	-0.779	Destabilizing	0.033	N	0.377	neutral	None	None	None	None	N
Q/V	0.2216	likely_benign	0.1971	benign	0.067	Stabilizing	0.033	N	0.415	neutral	None	None	None	None	N
Q/W	0.536	ambiguous	0.499	ambiguous	-0.098	Destabilizing	0.931	D	0.542	neutral	None	None	None	None	N
Q/Y	0.4204	ambiguous	0.3642	ambiguous	0.112	Stabilizing	0.076	N	0.512	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.