TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21412	64459;64460;64461	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
N2AB	19771	59536;59537;59538	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
N2A	18844	56755;56756;56757	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
N2B	12347	37264;37265;37266	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
Novex-1	12472	37639;37640;37641	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
Novex-2	12539	37840;37841;37842	chr2:178586667;178586666;178586665	chr2:179451394;179451393;179451392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-43
• Domain position: 47
• Structural Position: 62
• Q(SASA): 0.2396
• 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/S	None	None	0.625	N	0.494	0.233	0.18274738541	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.4806	ambiguous	0.4391	ambiguous	-0.683	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
A/D	0.1774	likely_benign	0.1595	benign	-0.789	Destabilizing	0.728	D	0.389	neutral	None	None	None	None	N
A/E	0.1655	likely_benign	0.1524	benign	-0.899	Destabilizing	0.005	N	0.259	neutral	N	0.360498442	None	None	N
A/F	0.3455	ambiguous	0.3214	benign	-0.89	Destabilizing	0.991	D	0.499	neutral	None	None	None	None	N
A/G	0.1203	likely_benign	0.1166	benign	-0.55	Destabilizing	0.012	N	0.216	neutral	N	0.389455912	None	None	N
A/H	0.3913	ambiguous	0.3564	ambiguous	-0.501	Destabilizing	0.993	D	0.497	neutral	None	None	None	None	N
A/I	0.1652	likely_benign	0.162	benign	-0.339	Destabilizing	0.974	D	0.443	neutral	None	None	None	None	N
A/K	0.3402	ambiguous	0.2847	benign	-0.82	Destabilizing	0.728	D	0.366	neutral	None	None	None	None	N
A/L	0.1292	likely_benign	0.1272	benign	-0.339	Destabilizing	0.842	D	0.389	neutral	None	None	None	None	N
A/M	0.173	likely_benign	0.1768	benign	-0.464	Destabilizing	0.998	D	0.475	neutral	None	None	None	None	N
A/N	0.1719	likely_benign	0.1618	benign	-0.491	Destabilizing	0.949	D	0.421	neutral	None	None	None	None	N
A/P	0.0999	likely_benign	0.0991	benign	-0.339	Destabilizing	0.966	D	0.415	neutral	N	0.412834204	None	None	N
A/Q	0.243	likely_benign	0.2288	benign	-0.734	Destabilizing	0.904	D	0.406	neutral	None	None	None	None	N
A/R	0.3938	ambiguous	0.3341	benign	-0.328	Destabilizing	0.949	D	0.415	neutral	None	None	None	None	N
A/S	0.0849	likely_benign	0.0837	benign	-0.678	Destabilizing	0.625	D	0.494	neutral	N	0.381316431	None	None	N
A/T	0.0779	likely_benign	0.0773	benign	-0.707	Destabilizing	0.801	D	0.443	neutral	N	0.403155928	None	None	N
A/V	0.0943	likely_benign	0.093	benign	-0.339	Destabilizing	0.891	D	0.445	neutral	N	0.443175754	None	None	N
A/W	0.6795	likely_pathogenic	0.6295	pathogenic	-1.083	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
A/Y	0.466	ambiguous	0.4165	ambiguous	-0.725	Destabilizing	0.991	D	0.5	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.