TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15991	48196;48197;48198	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
N2AB	14350	43273;43274;43275	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
N2A	13423	40492;40493;40494	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
N2B	6926	21001;21002;21003	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
Novex-1	7051	21376;21377;21378	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
Novex-2	7118	21577;21578;21579	chr2:178616918;178616917;178616916	chr2:179481645;179481644;179481643
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-109
• Domain position: 24
• Structural Position: 43
• Q(SASA): 0.7569
• 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
R/K	rs2057438704	None	0.468	N	0.28	0.141	0.18995819373	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
R/K	rs2057438704	None	0.468	N	0.28	0.141	0.18995819373	gnomAD-4.0.0	3.8489E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	4.02166E-05	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
R/A	0.1959	likely_benign	0.2271	benign	-0.587	Destabilizing	0.051	N	0.274	neutral	None	None	None	None	I
R/C	0.1454	likely_benign	0.1719	benign	-0.534	Destabilizing	0.968	D	0.453	neutral	None	None	None	None	I
R/D	0.531	ambiguous	0.5809	pathogenic	0.041	Stabilizing	0.738	D	0.528	neutral	None	None	None	None	I
R/E	0.2556	likely_benign	0.2981	benign	0.131	Stabilizing	0.538	D	0.299	neutral	None	None	None	None	I
R/F	0.366	ambiguous	0.4332	ambiguous	-0.643	Destabilizing	0.582	D	0.537	neutral	None	None	None	None	I
R/G	0.2607	likely_benign	0.2963	benign	-0.844	Destabilizing	0.468	N	0.411	neutral	N	0.510586158	None	None	I
R/H	0.1244	likely_benign	0.146	benign	-1.238	Destabilizing	0.968	D	0.359	neutral	None	None	None	None	I
R/I	0.1009	likely_benign	0.1362	benign	0.081	Stabilizing	0.002	N	0.207	neutral	None	None	None	None	I
R/K	0.0974	likely_benign	0.1079	benign	-0.577	Destabilizing	0.468	N	0.28	neutral	N	0.449847546	None	None	I
R/L	0.1277	likely_benign	0.1572	benign	0.081	Stabilizing	0.001	N	0.191	neutral	None	None	None	None	I
R/M	0.1542	likely_benign	0.1894	benign	-0.203	Destabilizing	0.786	D	0.445	neutral	N	0.511551841	None	None	I
R/N	0.3881	ambiguous	0.4416	ambiguous	-0.075	Destabilizing	0.738	D	0.355	neutral	None	None	None	None	I
R/P	0.2204	likely_benign	0.2347	benign	-0.121	Destabilizing	0.896	D	0.519	neutral	None	None	None	None	I
R/Q	0.1043	likely_benign	0.1183	benign	-0.271	Destabilizing	0.896	D	0.39	neutral	None	None	None	None	I
R/S	0.2821	likely_benign	0.3321	benign	-0.75	Destabilizing	0.178	N	0.359	neutral	N	0.487810275	None	None	I
R/T	0.1302	likely_benign	0.1622	benign	-0.499	Destabilizing	0.002	N	0.201	neutral	N	0.411410825	None	None	I
R/V	0.1356	likely_benign	0.1746	benign	-0.121	Destabilizing	0.001	N	0.207	neutral	None	None	None	None	I
R/W	0.2089	likely_benign	0.2421	benign	-0.429	Destabilizing	0.988	D	0.439	neutral	N	0.512448086	None	None	I
R/Y	0.3039	likely_benign	0.3443	ambiguous	-0.092	Destabilizing	0.738	D	0.505	neutral	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.