TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25971	78136;78137;78138	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
N2AB	24330	73213;73214;73215	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
N2A	23403	70432;70433;70434	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
N2B	16906	50941;50942;50943	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
Novex-1	17031	51316;51317;51318	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
Novex-2	17098	51517;51518;51519	chr2:178568221;178568220;178568219	chr2:179432948;179432947;179432946
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: Fn3-76
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5905
• Predicted PPI site: I

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/H	rs1432174919	0.057	0.999	N	0.595	0.41	0.297375071883	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
Y/H	rs1432174919	0.057	0.999	N	0.595	0.41	0.297375071883	gnomAD-4.0.0	1.02644E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.16947E-05	0	3.31422E-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
Y/A	0.982	likely_pathogenic	0.9763	pathogenic	-0.568	Destabilizing	0.996	D	0.652	neutral	None	None	None	None	I
Y/C	0.7268	likely_pathogenic	0.6477	pathogenic	0.25	Stabilizing	1.0	D	0.702	prob.neutral	N	0.520500387	None	None	I
Y/D	0.9811	likely_pathogenic	0.9786	pathogenic	0.783	Stabilizing	0.999	D	0.709	prob.delet.	N	0.496470798	None	None	I
Y/E	0.9945	likely_pathogenic	0.9931	pathogenic	0.759	Stabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	I
Y/F	0.1481	likely_benign	0.1397	benign	-0.308	Destabilizing	0.989	D	0.537	neutral	N	0.459721287	None	None	I
Y/G	0.9641	likely_pathogenic	0.9559	pathogenic	-0.751	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
Y/H	0.8067	likely_pathogenic	0.7721	pathogenic	0.244	Stabilizing	0.999	D	0.595	neutral	N	0.467454764	None	None	I
Y/I	0.9579	likely_pathogenic	0.9553	pathogenic	-0.111	Destabilizing	0.983	D	0.647	neutral	None	None	None	None	I
Y/K	0.9865	likely_pathogenic	0.9843	pathogenic	0.287	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
Y/L	0.8925	likely_pathogenic	0.8917	pathogenic	-0.111	Destabilizing	0.269	N	0.451	neutral	None	None	None	None	I
Y/M	0.9622	likely_pathogenic	0.9554	pathogenic	-0.011	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	I
Y/N	0.9041	likely_pathogenic	0.8752	pathogenic	0.113	Stabilizing	0.999	D	0.693	prob.neutral	N	0.473847092	None	None	I
Y/P	0.9974	likely_pathogenic	0.9971	pathogenic	-0.244	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
Y/Q	0.985	likely_pathogenic	0.9797	pathogenic	0.148	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
Y/R	0.9641	likely_pathogenic	0.9571	pathogenic	0.513	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
Y/S	0.9445	likely_pathogenic	0.9325	pathogenic	-0.261	Destabilizing	0.999	D	0.667	neutral	N	0.479380501	None	None	I
Y/T	0.9854	likely_pathogenic	0.9845	pathogenic	-0.193	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	I
Y/V	0.9204	likely_pathogenic	0.9127	pathogenic	-0.244	Destabilizing	0.983	D	0.636	neutral	None	None	None	None	I
Y/W	0.7386	likely_pathogenic	0.7166	pathogenic	-0.467	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	I

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.