TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25207	75844;75845;75846	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
N2AB	23566	70921;70922;70923	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
N2A	22639	68140;68141;68142	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
N2B	16142	48649;48650;48651	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
Novex-1	16267	49024;49025;49026	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
Novex-2	16334	49225;49226;49227	chr2:178570513;178570512;178570511	chr2:179435240;179435239;179435238
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-71
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3217
• Predicted PPI site: I

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
P/R	rs72646900	-0.823	0.957	N	0.886	0.422	0.439339381091	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	3.93E-05	0
P/R	rs72646900	-0.823	0.957	N	0.886	0.422	0.439339381091	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
P/R	rs72646900	-0.823	0.957	N	0.886	0.422	0.439339381091	gnomAD-4.0.0	2.16963E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88236E-05	0	1.60185E-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
P/A	0.1328	likely_benign	0.119	benign	-1.695	Destabilizing	0.865	D	0.804	deleterious	N	0.480939134	None	None	I
P/C	0.5473	ambiguous	0.5554	ambiguous	-1.097	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	I
P/D	0.8593	likely_pathogenic	0.8598	pathogenic	-1.832	Destabilizing	0.983	D	0.849	deleterious	None	None	None	None	I
P/E	0.5889	likely_pathogenic	0.5702	pathogenic	-1.825	Destabilizing	0.895	D	0.833	deleterious	None	None	None	None	I
P/F	0.6237	likely_pathogenic	0.6102	pathogenic	-1.311	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	I
P/G	0.6096	likely_pathogenic	0.6142	pathogenic	-2.019	Highly Destabilizing	0.983	D	0.859	deleterious	None	None	None	None	I
P/H	0.3704	ambiguous	0.3692	ambiguous	-1.588	Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	I
P/I	0.3895	ambiguous	0.3506	ambiguous	-0.889	Destabilizing	0.992	D	0.878	deleterious	None	None	None	None	I
P/K	0.3652	ambiguous	0.3676	ambiguous	-1.358	Destabilizing	0.968	D	0.847	deleterious	None	None	None	None	I
P/L	0.1857	likely_benign	0.172	benign	-0.889	Destabilizing	0.978	D	0.879	deleterious	D	0.524635274	None	None	I
P/M	0.3915	ambiguous	0.3725	ambiguous	-0.678	Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	I
P/N	0.6862	likely_pathogenic	0.6865	pathogenic	-1.155	Destabilizing	0.983	D	0.879	deleterious	None	None	None	None	I
P/Q	0.2778	likely_benign	0.2675	benign	-1.352	Destabilizing	0.476	N	0.589	neutral	N	0.511339958	None	None	I
P/R	0.2662	likely_benign	0.2621	benign	-0.836	Destabilizing	0.957	D	0.886	deleterious	N	0.518594886	None	None	I
P/S	0.2914	likely_benign	0.269	benign	-1.644	Destabilizing	0.957	D	0.849	deleterious	N	0.498413489	None	None	I
P/T	0.2741	likely_benign	0.2451	benign	-1.539	Destabilizing	0.978	D	0.845	deleterious	N	0.510138643	None	None	I
P/V	0.3032	likely_benign	0.273	benign	-1.125	Destabilizing	0.983	D	0.879	deleterious	None	None	None	None	I
P/W	0.8291	likely_pathogenic	0.8323	pathogenic	-1.522	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	I
P/Y	0.659	likely_pathogenic	0.639	pathogenic	-1.249	Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	I

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.