TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28743	86452;86453;86454	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
N2AB	27102	81529;81530;81531	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
N2A	26175	78748;78749;78750	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
N2B	19678	59257;59258;59259	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
Novex-1	19803	59632;59633;59634	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
Novex-2	19870	59833;59834;59835	chr2:178559905;178559904;178559903	chr2:179424632;179424631;179424630
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: Fn3-97
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.2723
• 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
Q/R	None	None	0.651	N	0.498	0.143	0.186928172975	gnomAD-4.0.0	4.79018E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29649E-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	0.228	likely_benign	0.234	benign	-0.714	Destabilizing	0.505	D	0.501	neutral	None	None	None	None	N
Q/C	0.4721	ambiguous	0.5109	ambiguous	-0.141	Destabilizing	0.995	D	0.635	neutral	None	None	None	None	N
Q/D	0.7064	likely_pathogenic	0.6854	pathogenic	-1.046	Destabilizing	0.712	D	0.463	neutral	None	None	None	None	N
Q/E	0.1263	likely_benign	0.1139	benign	-0.824	Destabilizing	0.435	N	0.488	neutral	N	0.466805973	None	None	N
Q/F	0.641	likely_pathogenic	0.6481	pathogenic	-0.14	Destabilizing	0.946	D	0.606	neutral	None	None	None	None	N
Q/G	0.4249	ambiguous	0.4279	ambiguous	-1.166	Destabilizing	0.712	D	0.497	neutral	None	None	None	None	N
Q/H	0.2288	likely_benign	0.245	benign	-0.756	Destabilizing	0.013	N	0.273	neutral	N	0.467312952	None	None	N
Q/I	0.3029	likely_benign	0.304	benign	0.497	Stabilizing	0.553	D	0.593	neutral	None	None	None	None	N
Q/K	0.1565	likely_benign	0.1573	benign	-0.301	Destabilizing	0.651	D	0.495	neutral	N	0.466298994	None	None	N
Q/L	0.1676	likely_benign	0.1716	benign	0.497	Stabilizing	0.483	N	0.512	neutral	N	0.500428972	None	None	N
Q/M	0.3742	ambiguous	0.3766	ambiguous	0.742	Stabilizing	0.946	D	0.499	neutral	None	None	None	None	N
Q/N	0.4685	ambiguous	0.4747	ambiguous	-1.131	Destabilizing	0.712	D	0.479	neutral	None	None	None	None	N
Q/P	0.4579	ambiguous	0.5045	ambiguous	0.124	Stabilizing	0.976	D	0.543	neutral	N	0.467566442	None	None	N
Q/R	0.1535	likely_benign	0.1612	benign	-0.404	Destabilizing	0.651	D	0.498	neutral	N	0.464524567	None	None	N
Q/S	0.3595	ambiguous	0.3703	ambiguous	-1.312	Destabilizing	0.712	D	0.437	neutral	None	None	None	None	N
Q/T	0.2464	likely_benign	0.2587	benign	-0.875	Destabilizing	0.712	D	0.474	neutral	None	None	None	None	N
Q/V	0.175	likely_benign	0.1773	benign	0.124	Stabilizing	0.032	N	0.416	neutral	None	None	None	None	N
Q/W	0.6057	likely_pathogenic	0.624	pathogenic	-0.09	Destabilizing	0.995	D	0.611	neutral	None	None	None	None	N
Q/Y	0.4103	ambiguous	0.4285	ambiguous	0.231	Stabilizing	0.897	D	0.539	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.