TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6743	20452;20453;20454	chr2:178727138;178727137;178727136	chr2:179591865;179591864;179591863
N2AB	6426	19501;19502;19503	chr2:178727138;178727137;178727136	chr2:179591865;179591864;179591863
N2A	5499	16720;16721;16722	chr2:178727138;178727137;178727136	chr2:179591865;179591864;179591863
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-51
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.5671
• 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
Q/H	rs1354673910	-0.683	None	N	0.115	0.131	0.154104182512	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.01E-06	0
Q/H	rs1354673910	-0.683	None	N	0.115	0.131	0.154104182512	gnomAD-4.0.0	5.51483E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.24158E-06	0	0
Q/R	rs794729620	None	0.001	N	0.12	0.08	0.119812018005	gnomAD-4.0.0	1.37835E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.81002E-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
Q/A	0.261	likely_benign	0.2478	benign	-0.493	Destabilizing	0.002	N	0.155	neutral	None	None	None	None	I
Q/C	0.4531	ambiguous	0.4416	ambiguous	-0.169	Destabilizing	0.859	D	0.467	neutral	None	None	None	None	I
Q/D	0.4118	ambiguous	0.404	ambiguous	-1.321	Destabilizing	0.104	N	0.267	neutral	None	None	None	None	I
Q/E	0.0917	likely_benign	0.0938	benign	-1.22	Destabilizing	0.042	N	0.241	neutral	N	0.463850175	None	None	I
Q/F	0.4767	ambiguous	0.4727	ambiguous	-0.281	Destabilizing	0.497	N	0.511	neutral	None	None	None	None	I
Q/G	0.296	likely_benign	0.2847	benign	-0.843	Destabilizing	0.055	N	0.411	neutral	None	None	None	None	I
Q/H	0.1128	likely_benign	0.113	benign	-0.889	Destabilizing	None	N	0.115	neutral	N	0.450211661	None	None	I
Q/I	0.3164	likely_benign	0.3009	benign	0.396	Stabilizing	0.124	N	0.5	neutral	None	None	None	None	I
Q/K	0.0846	likely_benign	0.0872	benign	-0.43	Destabilizing	0.042	N	0.289	neutral	N	0.470141429	None	None	I
Q/L	0.1315	likely_benign	0.1265	benign	0.396	Stabilizing	0.042	N	0.401	neutral	N	0.501792488	None	None	I
Q/M	0.3642	ambiguous	0.3534	ambiguous	0.802	Stabilizing	0.667	D	0.399	neutral	None	None	None	None	I
Q/N	0.2613	likely_benign	0.2535	benign	-1.011	Destabilizing	0.055	N	0.263	neutral	None	None	None	None	I
Q/P	0.7441	likely_pathogenic	0.7414	pathogenic	0.131	Stabilizing	0.301	N	0.45	neutral	N	0.492151244	None	None	I
Q/R	0.0715	likely_benign	0.0729	benign	-0.379	Destabilizing	0.001	N	0.12	neutral	N	0.455540123	None	None	I
Q/S	0.2381	likely_benign	0.2282	benign	-1.03	Destabilizing	0.002	N	0.107	neutral	None	None	None	None	I
Q/T	0.1868	likely_benign	0.1835	benign	-0.754	Destabilizing	0.055	N	0.382	neutral	None	None	None	None	I
Q/V	0.2156	likely_benign	0.2114	benign	0.131	Stabilizing	0.004	N	0.253	neutral	None	None	None	None	I
Q/W	0.3129	likely_benign	0.3229	benign	-0.253	Destabilizing	0.958	D	0.465	neutral	None	None	None	None	I
Q/Y	0.275	likely_benign	0.2702	benign	0.051	Stabilizing	0.124	N	0.492	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.