TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28800	86623;86624;86625	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
N2AB	27159	81700;81701;81702	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
N2A	26232	78919;78920;78921	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
N2B	19735	59428;59429;59430	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
Novex-1	19860	59803;59804;59805	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
Novex-2	19927	60004;60005;60006	chr2:178559734;178559733;178559732	chr2:179424461;179424460;179424459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-144
• Domain position: 46
• Structural Position: 122
• Q(SASA): 0.5058
• 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
Y/S	None	None	None	N	0.156	0.201	0.370240404367	gnomAD-4.0.0	1.38188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05581E-07	1.19574E-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
Y/A	0.1331	likely_benign	0.1796	benign	-0.56	Destabilizing	None	N	0.157	neutral	None	None	None	None	N
Y/C	0.0629	likely_benign	0.0751	benign	0.114	Stabilizing	None	N	0.249	neutral	N	0.449075511	None	None	N
Y/D	0.1166	likely_benign	0.1624	benign	0.923	Stabilizing	None	N	0.212	neutral	N	0.379079495	None	None	N
Y/E	0.2859	likely_benign	0.379	ambiguous	0.902	Stabilizing	0.033	N	0.291	neutral	None	None	None	None	N
Y/F	0.0615	likely_benign	0.0657	benign	-0.252	Destabilizing	0.202	N	0.319	neutral	N	0.411903989	None	None	N
Y/G	0.1655	likely_benign	0.2283	benign	-0.739	Destabilizing	None	N	0.197	neutral	None	None	None	None	N
Y/H	0.0872	likely_benign	0.1102	benign	0.279	Stabilizing	0.47	N	0.314	neutral	N	0.368017139	None	None	N
Y/I	0.1322	likely_benign	0.1726	benign	-0.118	Destabilizing	0.033	N	0.282	neutral	None	None	None	None	N
Y/K	0.261	likely_benign	0.3528	ambiguous	0.23	Stabilizing	0.033	N	0.275	neutral	None	None	None	None	N
Y/L	0.1858	likely_benign	0.235	benign	-0.118	Destabilizing	0.015	N	0.235	neutral	None	None	None	None	N
Y/M	0.2444	likely_benign	0.295	benign	-0.051	Destabilizing	0.54	D	0.263	neutral	None	None	None	None	N
Y/N	0.0631	likely_benign	0.0842	benign	0.018	Stabilizing	None	N	0.178	neutral	N	0.347428436	None	None	N
Y/P	0.8058	likely_pathogenic	0.8665	pathogenic	-0.246	Destabilizing	0.251	N	0.404	neutral	None	None	None	None	N
Y/Q	0.1936	likely_benign	0.2562	benign	0.076	Stabilizing	0.142	N	0.376	neutral	None	None	None	None	N
Y/R	0.1694	likely_benign	0.235	benign	0.446	Stabilizing	0.142	N	0.395	neutral	None	None	None	None	N
Y/S	0.0561	likely_benign	0.0744	benign	-0.389	Destabilizing	None	N	0.156	neutral	N	0.35119946	None	None	N
Y/T	0.0964	likely_benign	0.1314	benign	-0.32	Destabilizing	0.015	N	0.3	neutral	None	None	None	None	N
Y/V	0.111	likely_benign	0.1383	benign	-0.246	Destabilizing	None	N	0.158	neutral	None	None	None	None	N
Y/W	0.2692	likely_benign	0.3012	benign	-0.402	Destabilizing	0.781	D	0.341	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.