TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24972	75139;75140;75141	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
N2AB	23331	70216;70217;70218	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
N2A	22404	67435;67436;67437	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
N2B	15907	47944;47945;47946	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
Novex-1	16032	48319;48320;48321	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
Novex-2	16099	48520;48521;48522	chr2:178571218;178571217;178571216	chr2:179435945;179435944;179435943
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-69
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.467
• 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
G/S	None	None	0.997	N	0.745	0.343	0.241664281697	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
G/A	0.16	likely_benign	0.1568	benign	-0.423	Destabilizing	0.995	D	0.653	neutral	N	0.50804241	None	None	N
G/C	0.2211	likely_benign	0.2003	benign	-0.865	Destabilizing	1.0	D	0.777	deleterious	D	0.538770418	None	None	N
G/D	0.2473	likely_benign	0.2779	benign	-0.49	Destabilizing	0.997	D	0.784	deleterious	N	0.507381948	None	None	N
G/E	0.3227	likely_benign	0.3627	ambiguous	-0.634	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
G/F	0.5891	likely_pathogenic	0.5827	pathogenic	-1.069	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
G/H	0.4234	ambiguous	0.411	ambiguous	-0.696	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/I	0.4351	ambiguous	0.4211	ambiguous	-0.445	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/K	0.5716	likely_pathogenic	0.5865	pathogenic	-0.838	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
G/L	0.4515	ambiguous	0.4443	ambiguous	-0.445	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
G/M	0.4687	ambiguous	0.4532	ambiguous	-0.465	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
G/N	0.2184	likely_benign	0.2198	benign	-0.481	Destabilizing	0.669	D	0.514	neutral	None	None	None	None	N
G/P	0.8236	likely_pathogenic	0.8264	pathogenic	-0.402	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
G/Q	0.3852	ambiguous	0.3921	ambiguous	-0.744	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/R	0.4543	ambiguous	0.4681	ambiguous	-0.415	Destabilizing	0.999	D	0.799	deleterious	N	0.477518666	None	None	N
G/S	0.111	likely_benign	0.1117	benign	-0.68	Destabilizing	0.997	D	0.745	deleterious	N	0.511425117	None	None	N
G/T	0.2086	likely_benign	0.2074	benign	-0.743	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
G/V	0.3177	likely_benign	0.3128	benign	-0.402	Destabilizing	0.999	D	0.816	deleterious	D	0.526907134	None	None	N
G/W	0.5068	ambiguous	0.4969	ambiguous	-1.242	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
G/Y	0.4726	ambiguous	0.4544	ambiguous	-0.875	Destabilizing	1.0	D	0.823	deleterious	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.