TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7021	21286;21287;21288	chr2:178724314;178724313;178724312	chr2:179589041;179589040;179589039
N2AB	6704	20335;20336;20337	chr2:178724314;178724313;178724312	chr2:179589041;179589040;179589039
N2A	5777	17554;17555;17556	chr2:178724314;178724313;178724312	chr2:179589041;179589040;179589039
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-54
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.1436
• 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/H	rs757015621	-1.508	0.927	N	0.587	0.381	0.257292322809	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.55E-05	0
Q/H	rs757015621	-1.508	0.927	N	0.587	0.381	0.257292322809	gnomAD-4.0.0	1.30028E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52932E-05	2.31927E-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	0.243	likely_benign	0.2788	benign	-1.092	Destabilizing	0.001	N	0.315	neutral	None	None	None	None	N
Q/C	0.5653	likely_pathogenic	0.5898	pathogenic	-0.497	Destabilizing	0.981	D	0.621	neutral	None	None	None	None	N
Q/D	0.4981	ambiguous	0.567	pathogenic	-1.614	Destabilizing	0.329	N	0.389	neutral	None	None	None	None	N
Q/E	0.078	likely_benign	0.0868	benign	-1.336	Destabilizing	0.001	N	0.181	neutral	N	0.388893843	None	None	N
Q/F	0.6598	likely_pathogenic	0.7065	pathogenic	-0.496	Destabilizing	0.944	D	0.655	neutral	None	None	None	None	N
Q/G	0.4344	ambiguous	0.4835	ambiguous	-1.553	Destabilizing	0.176	N	0.525	neutral	None	None	None	None	N
Q/H	0.1869	likely_benign	0.2094	benign	-1.01	Destabilizing	0.927	D	0.587	neutral	N	0.494869302	None	None	N
Q/I	0.2802	likely_benign	0.314	benign	0.167	Stabilizing	0.704	D	0.625	neutral	None	None	None	None	N
Q/K	0.1054	likely_benign	0.1111	benign	-0.356	Destabilizing	0.01	N	0.219	neutral	N	0.430335034	None	None	N
Q/L	0.1219	likely_benign	0.1394	benign	0.167	Stabilizing	0.425	N	0.548	neutral	N	0.43966938	None	None	N
Q/M	0.3336	likely_benign	0.3822	ambiguous	0.353	Stabilizing	0.981	D	0.58	neutral	None	None	None	None	N
Q/N	0.3817	ambiguous	0.4347	ambiguous	-1.233	Destabilizing	0.495	N	0.484	neutral	None	None	None	None	N
Q/P	0.9101	likely_pathogenic	0.9168	pathogenic	-0.226	Destabilizing	0.784	D	0.579	neutral	N	0.485291617	None	None	N
Q/R	0.0954	likely_benign	0.0979	benign	-0.488	Destabilizing	0.002	N	0.27	neutral	N	0.378388848	None	None	N
Q/S	0.2852	likely_benign	0.3236	benign	-1.517	Destabilizing	0.037	N	0.213	neutral	None	None	None	None	N
Q/T	0.1944	likely_benign	0.2214	benign	-1.031	Destabilizing	0.329	N	0.491	neutral	None	None	None	None	N
Q/V	0.1862	likely_benign	0.2131	benign	-0.226	Destabilizing	0.329	N	0.557	neutral	None	None	None	None	N
Q/W	0.4967	ambiguous	0.5179	ambiguous	-0.446	Destabilizing	0.995	D	0.598	neutral	None	None	None	None	N
Q/Y	0.452	ambiguous	0.4942	ambiguous	-0.09	Destabilizing	0.981	D	0.601	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.