TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8886	26881;26882;26883	chr2:178714002;178714001;178714000	chr2:179578729;179578728;179578727
N2AB	8569	25930;25931;25932	chr2:178714002;178714001;178714000	chr2:179578729;179578728;179578727
N2A	7642	23149;23150;23151	chr2:178714002;178714001;178714000	chr2:179578729;179578728;179578727
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-74
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1332
• 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/D	None	None	0.801	N	0.683	0.299	0.261217442401	gnomAD-4.0.0	2.40069E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62506E-06	0	0
G/S	rs72648991	-1.142	0.233	N	0.269	0.188	0.156986980423	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
G/S	rs72648991	-1.142	0.233	N	0.269	0.188	0.156986980423	gnomAD-4.0.0	2.2582E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7337E-04	2.69863E-05	1.1598E-05	1.65711E-05

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	0.0871	likely_benign	0.0931	benign	-0.519	Destabilizing	0.454	N	0.544	neutral	N	0.444976413	None	None	N
G/C	0.1408	likely_benign	0.1542	benign	-0.958	Destabilizing	0.145	N	0.665	neutral	N	0.486228389	None	None	N
G/D	0.4367	ambiguous	0.5001	ambiguous	-1.491	Destabilizing	0.801	D	0.683	prob.neutral	N	0.440109311	None	None	N
G/E	0.3044	likely_benign	0.3545	ambiguous	-1.359	Destabilizing	0.842	D	0.684	prob.neutral	None	None	None	None	N
G/F	0.4554	ambiguous	0.4968	ambiguous	-0.575	Destabilizing	0.037	N	0.664	neutral	None	None	None	None	N
G/H	0.3675	ambiguous	0.4015	ambiguous	-1.655	Destabilizing	0.998	D	0.662	neutral	None	None	None	None	N
G/I	0.1698	likely_benign	0.1934	benign	0.483	Stabilizing	0.949	D	0.686	prob.neutral	None	None	None	None	N
G/K	0.4696	ambiguous	0.5247	ambiguous	-0.838	Destabilizing	0.842	D	0.683	prob.neutral	None	None	None	None	N
G/L	0.2785	likely_benign	0.3113	benign	0.483	Stabilizing	0.728	D	0.703	prob.neutral	None	None	None	None	N
G/M	0.3064	likely_benign	0.3347	benign	0.134	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
G/N	0.3136	likely_benign	0.3439	ambiguous	-0.947	Destabilizing	0.842	D	0.655	neutral	None	None	None	None	N
G/P	0.9672	likely_pathogenic	0.9734	pathogenic	0.195	Stabilizing	0.974	D	0.673	neutral	None	None	None	None	N
G/Q	0.3202	likely_benign	0.3623	ambiguous	-0.814	Destabilizing	0.974	D	0.68	prob.neutral	None	None	None	None	N
G/R	0.3183	likely_benign	0.3629	ambiguous	-1.024	Destabilizing	0.986	D	0.68	prob.neutral	N	0.433047265	None	None	N
G/S	0.0782	likely_benign	0.0824	benign	-1.332	Destabilizing	0.233	N	0.269	neutral	N	0.353103615	None	None	N
G/T	0.1	likely_benign	0.1034	benign	-1.075	Destabilizing	0.067	N	0.497	neutral	None	None	None	None	N
G/V	0.1248	likely_benign	0.1441	benign	0.195	Stabilizing	0.669	D	0.707	prob.neutral	N	0.419368679	None	None	N
G/W	0.3834	ambiguous	0.4342	ambiguous	-1.31	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
G/Y	0.3518	ambiguous	0.4138	ambiguous	-0.679	Destabilizing	0.904	D	0.705	prob.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.