TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28111	84556;84557;84558	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
N2AB	26470	79633;79634;79635	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
N2A	25543	76852;76853;76854	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
N2B	19046	57361;57362;57363	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
Novex-1	19171	57736;57737;57738	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
Novex-2	19238	57937;57938;57939	chr2:178561801;178561800;178561799	chr2:179426528;179426527;179426526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-92
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.6598
• 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
R/K	rs1060500463	None	0.773	N	0.517	0.2	0.335910606209	gnomAD-4.0.0	3.1835E-06	None	None	None	None	N	None	5.65675E-05	0	None	0	0	None	0	0	0	0	3.02499E-05

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
R/A	0.9163	likely_pathogenic	0.9172	pathogenic	0.044	Stabilizing	0.845	D	0.572	neutral	None	None	None	None	N
R/C	0.5758	likely_pathogenic	0.6004	pathogenic	-0.207	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/D	0.9623	likely_pathogenic	0.9675	pathogenic	-0.199	Destabilizing	0.975	D	0.594	neutral	None	None	None	None	N
R/E	0.8774	likely_pathogenic	0.8899	pathogenic	-0.152	Destabilizing	0.916	D	0.578	neutral	None	None	None	None	N
R/F	0.9465	likely_pathogenic	0.9472	pathogenic	-0.252	Destabilizing	0.987	D	0.648	neutral	None	None	None	None	N
R/G	0.7328	likely_pathogenic	0.7665	pathogenic	-0.111	Destabilizing	0.892	D	0.542	neutral	N	0.521020462	None	None	N
R/H	0.4139	ambiguous	0.4071	ambiguous	-0.584	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
R/I	0.9063	likely_pathogenic	0.905	pathogenic	0.408	Stabilizing	0.967	D	0.653	neutral	N	0.486510525	None	None	N
R/K	0.3358	likely_benign	0.3367	benign	-0.099	Destabilizing	0.773	D	0.517	neutral	N	0.482558074	None	None	N
R/L	0.8064	likely_pathogenic	0.8042	pathogenic	0.408	Stabilizing	0.845	D	0.558	neutral	None	None	None	None	N
R/M	0.8578	likely_pathogenic	0.861	pathogenic	-0.026	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
R/N	0.9468	likely_pathogenic	0.9477	pathogenic	0.018	Stabilizing	0.975	D	0.602	neutral	None	None	None	None	N
R/P	0.9735	likely_pathogenic	0.9767	pathogenic	0.305	Stabilizing	0.987	D	0.659	neutral	None	None	None	None	N
R/Q	0.4059	ambiguous	0.4153	ambiguous	-0.038	Destabilizing	0.987	D	0.612	neutral	None	None	None	None	N
R/S	0.929	likely_pathogenic	0.933	pathogenic	-0.219	Destabilizing	0.805	D	0.586	neutral	N	0.475016026	None	None	N
R/T	0.8639	likely_pathogenic	0.8768	pathogenic	-0.057	Destabilizing	0.025	N	0.361	neutral	N	0.486883671	None	None	N
R/V	0.9164	likely_pathogenic	0.919	pathogenic	0.305	Stabilizing	0.95	D	0.573	neutral	None	None	None	None	N
R/W	0.6182	likely_pathogenic	0.6282	pathogenic	-0.4	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
R/Y	0.866	likely_pathogenic	0.8614	pathogenic	0.015	Stabilizing	0.996	D	0.653	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.