TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19848	59767;59768;59769	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
N2AB	18207	54844;54845;54846	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
N2A	17280	52063;52064;52065	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
N2B	10783	32572;32573;32574	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
Novex-1	10908	32947;32948;32949	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
Novex-2	10975	33148;33149;33150	chr2:178592463;178592462;178592461	chr2:179457190;179457189;179457188
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-119
• Domain position: 59
• Structural Position: 145
• Q(SASA): 0.2349
• 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
A/D	None	None	0.213	N	0.429	0.198	0.373537453441	gnomAD-4.0.0	6.84324E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99594E-07	0	0
A/V	rs776318202	-0.182	0.001	N	0.129	0.069	0.245660935333	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/V	rs776318202	-0.182	0.001	N	0.129	0.069	0.245660935333	gnomAD-4.0.0	6.84324E-07	None	None	None	None	N	None	0	2.23664E-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
A/C	0.2998	likely_benign	0.282	benign	-0.83	Destabilizing	0.951	D	0.415	neutral	None	None	None	None	N
A/D	0.1931	likely_benign	0.1884	benign	-1.391	Destabilizing	0.213	N	0.429	neutral	N	0.45392397	None	None	N
A/E	0.1698	likely_benign	0.1621	benign	-1.522	Destabilizing	0.002	N	0.245	neutral	None	None	None	None	N
A/F	0.2454	likely_benign	0.2333	benign	-1.311	Destabilizing	0.557	D	0.441	neutral	None	None	None	None	N
A/G	0.1163	likely_benign	0.1143	benign	-0.934	Destabilizing	0.183	N	0.306	neutral	N	0.469605498	None	None	N
A/H	0.3116	likely_benign	0.2952	benign	-1.01	Destabilizing	0.836	D	0.46	neutral	None	None	None	None	N
A/I	0.1466	likely_benign	0.1319	benign	-0.643	Destabilizing	0.11	N	0.404	neutral	None	None	None	None	N
A/K	0.2545	likely_benign	0.2351	benign	-1.141	Destabilizing	0.264	N	0.413	neutral	None	None	None	None	N
A/L	0.1139	likely_benign	0.1065	benign	-0.643	Destabilizing	0.002	N	0.195	neutral	None	None	None	None	N
A/M	0.151	likely_benign	0.1375	benign	-0.356	Destabilizing	0.716	D	0.439	neutral	None	None	None	None	N
A/N	0.1472	likely_benign	0.1394	benign	-0.77	Destabilizing	0.01	N	0.168	neutral	None	None	None	None	N
A/P	0.4727	ambiguous	0.4353	ambiguous	-0.662	Destabilizing	0.794	D	0.428	neutral	N	0.486973457	None	None	N
A/Q	0.197	likely_benign	0.1879	benign	-1.115	Destabilizing	0.557	D	0.443	neutral	None	None	None	None	N
A/R	0.231	likely_benign	0.2323	benign	-0.567	Destabilizing	0.005	N	0.269	neutral	None	None	None	None	N
A/S	0.0739	likely_benign	0.0777	benign	-0.956	Destabilizing	0.101	N	0.327	neutral	N	0.428161521	None	None	N
A/T	0.0639	likely_benign	0.0625	benign	-1.022	Destabilizing	0.007	N	0.207	neutral	N	0.398628048	None	None	N
A/V	0.0853	likely_benign	0.0827	benign	-0.662	Destabilizing	0.001	N	0.129	neutral	N	0.433858129	None	None	N
A/W	0.6199	likely_pathogenic	0.6025	pathogenic	-1.482	Destabilizing	0.983	D	0.514	neutral	None	None	None	None	N
A/Y	0.3794	ambiguous	0.3629	ambiguous	-1.155	Destabilizing	0.836	D	0.451	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.