TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15626	47101;47102;47103	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
N2AB	13985	42178;42179;42180	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
N2A	13058	39397;39398;39399	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
N2B	6561	19906;19907;19908	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
Novex-1	6686	20281;20282;20283	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
Novex-2	6753	20482;20483;20484	chr2:178618674;178618673;178618672	chr2:179483401;179483400;179483399
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-108
• Domain position: 59
• Structural Position: 143
• Q(SASA): 0.6842
• 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
E/G	rs753479822	-0.283	0.22	N	0.493	0.088	0.239305524855	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/G	rs753479822	-0.283	0.22	N	0.493	0.088	0.239305524855	gnomAD-4.0.0	1.59455E-06	None	None	None	None	N	None	0	2.292E-05	None	0	0	None	0	0	0	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
E/A	0.1431	likely_benign	0.1905	benign	-0.633	Destabilizing	0.124	N	0.455	neutral	N	0.451787431	None	None	N
E/C	0.7592	likely_pathogenic	0.8551	pathogenic	-0.29	Destabilizing	0.968	D	0.651	neutral	None	None	None	None	N
E/D	0.0895	likely_benign	0.117	benign	-0.494	Destabilizing	None	N	0.2	neutral	N	0.443306031	None	None	N
E/F	0.6763	likely_pathogenic	0.7766	pathogenic	-0.359	Destabilizing	0.89	D	0.569	neutral	None	None	None	None	N
E/G	0.1709	likely_benign	0.2288	benign	-0.875	Destabilizing	0.22	N	0.493	neutral	N	0.447663064	None	None	N
E/H	0.364	ambiguous	0.4936	ambiguous	-0.259	Destabilizing	0.726	D	0.393	neutral	None	None	None	None	N
E/I	0.3917	ambiguous	0.5311	ambiguous	-0.009	Destabilizing	0.726	D	0.565	neutral	None	None	None	None	N
E/K	0.1768	likely_benign	0.242	benign	-0.092	Destabilizing	0.001	N	0.25	neutral	N	0.445950836	None	None	N
E/L	0.3788	ambiguous	0.5408	ambiguous	-0.009	Destabilizing	0.567	D	0.512	neutral	None	None	None	None	N
E/M	0.4446	ambiguous	0.5959	pathogenic	0.147	Stabilizing	0.968	D	0.537	neutral	None	None	None	None	N
E/N	0.1798	likely_benign	0.2363	benign	-0.427	Destabilizing	0.272	N	0.453	neutral	None	None	None	None	N
E/P	0.6763	likely_pathogenic	0.7902	pathogenic	-0.197	Destabilizing	0.726	D	0.444	neutral	None	None	None	None	N
E/Q	0.1486	likely_benign	0.1867	benign	-0.367	Destabilizing	0.124	N	0.472	neutral	N	0.451179941	None	None	N
E/R	0.2815	likely_benign	0.3583	ambiguous	0.189	Stabilizing	0.157	N	0.439	neutral	None	None	None	None	N
E/S	0.1664	likely_benign	0.224	benign	-0.633	Destabilizing	0.157	N	0.435	neutral	None	None	None	None	N
E/T	0.1839	likely_benign	0.2621	benign	-0.439	Destabilizing	0.272	N	0.479	neutral	None	None	None	None	N
E/V	0.2285	likely_benign	0.3152	benign	-0.197	Destabilizing	0.497	N	0.483	neutral	N	0.454893113	None	None	N
E/W	0.8355	likely_pathogenic	0.9069	pathogenic	-0.154	Destabilizing	0.968	D	0.684	prob.neutral	None	None	None	None	N
E/Y	0.5186	ambiguous	0.6419	pathogenic	-0.125	Destabilizing	0.726	D	0.533	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.