TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29722	89389;89390;89391	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
N2AB	28081	84466;84467;84468	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
N2A	27154	81685;81686;81687	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
N2B	20657	62194;62195;62196	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
Novex-1	20782	62569;62570;62571	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
Novex-2	20849	62770;62771;62772	chr2:178553947;178553946;178553945	chr2:179418674;179418673;179418672
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: Fn3-104
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.3037
• 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
P/A	None	None	0.001	N	0.276	0.084	0.139678290688	gnomAD-4.0.0	2.06279E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70283E-06	0	0
P/Q	rs763050858	-1.191	0.93	N	0.584	0.347	0.371344866733	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.38E-05	None	0	0	0
P/Q	rs763050858	-1.191	0.93	N	0.584	0.347	0.371344866733	gnomAD-4.0.0	1.61136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45062E-05	0
P/S	None	None	0.278	N	0.463	0.097	0.148003135375	gnomAD-4.0.0	2.75038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60378E-06	0	0
P/T	rs538120743	-1.411	0.435	N	0.495	0.106	0.253726318573	gnomAD-2.1.1	3.7E-05	None	None	None	None	N	None	0	2.05713E-04	None	0	0	None	3.36E-05	None	0	9E-06	0
P/T	rs538120743	-1.411	0.435	N	0.495	0.106	0.253726318573	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/T	rs538120743	-1.411	0.435	N	0.495	0.106	0.253726318573	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
P/T	rs538120743	-1.411	0.435	N	0.495	0.106	0.253726318573	gnomAD-4.0.0	1.12034E-05	None	None	None	None	N	None	0	1.17576E-04	None	0	0	None	0	0	6.79131E-06	3.32145E-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
P/A	0.0658	likely_benign	0.0624	benign	-1.518	Destabilizing	0.001	N	0.276	neutral	N	0.488155895	None	None	N
P/C	0.4993	ambiguous	0.5199	ambiguous	-0.907	Destabilizing	0.946	D	0.704	prob.delet.	None	None	None	None	N
P/D	0.7001	likely_pathogenic	0.6844	pathogenic	-1.112	Destabilizing	0.834	D	0.537	neutral	None	None	None	None	N
P/E	0.4128	ambiguous	0.4217	ambiguous	-1.088	Destabilizing	0.712	D	0.564	neutral	None	None	None	None	N
P/F	0.6391	likely_pathogenic	0.66	pathogenic	-1.13	Destabilizing	0.946	D	0.711	prob.delet.	None	None	None	None	N
P/G	0.4213	ambiguous	0.4008	ambiguous	-1.858	Destabilizing	0.338	N	0.523	neutral	None	None	None	None	N
P/H	0.4418	ambiguous	0.4627	ambiguous	-1.326	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
P/I	0.2499	likely_benign	0.2593	benign	-0.675	Destabilizing	0.553	D	0.626	neutral	None	None	None	None	N
P/K	0.5634	ambiguous	0.6017	pathogenic	-1.067	Destabilizing	0.712	D	0.549	neutral	None	None	None	None	N
P/L	0.1781	likely_benign	0.1814	benign	-0.675	Destabilizing	0.278	N	0.54	neutral	N	0.504240068	None	None	N
P/M	0.3106	likely_benign	0.3197	benign	-0.511	Destabilizing	0.946	D	0.656	prob.neutral	None	None	None	None	N
P/N	0.4949	ambiguous	0.5031	ambiguous	-0.89	Destabilizing	0.946	D	0.681	prob.neutral	None	None	None	None	N
P/Q	0.2967	likely_benign	0.3181	benign	-1.033	Destabilizing	0.93	D	0.584	neutral	N	0.507208446	None	None	N
P/R	0.4849	ambiguous	0.5115	ambiguous	-0.591	Destabilizing	0.93	D	0.679	prob.neutral	N	0.495598651	None	None	N
P/S	0.1729	likely_benign	0.1696	benign	-1.478	Destabilizing	0.278	N	0.463	neutral	N	0.499546324	None	None	N
P/T	0.1209	likely_benign	0.1199	benign	-1.339	Destabilizing	0.435	N	0.495	neutral	N	0.500815761	None	None	N
P/V	0.1702	likely_benign	0.1707	benign	-0.921	Destabilizing	0.014	N	0.404	neutral	None	None	None	None	N
P/W	0.8554	likely_pathogenic	0.8653	pathogenic	-1.321	Destabilizing	0.995	D	0.739	deleterious	None	None	None	None	N
P/Y	0.6425	likely_pathogenic	0.6698	pathogenic	-1.013	Destabilizing	0.982	D	0.71	prob.delet.	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.