TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17748	53467;53468;53469	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
N2AB	16107	48544;48545;48546	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
N2A	15180	45763;45764;45765	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
N2B	8683	26272;26273;26274	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
Novex-1	8808	26647;26648;26649	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
Novex-2	8875	26848;26849;26850	chr2:178607446;178607445;178607444	chr2:179472173;179472172;179472171
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-113
• Domain position: 72
• Structural Position: 161
• Q(SASA): 0.1959
• 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
N/D	rs1279556849	-0.999	0.999	D	0.635	0.684	0.358948522604	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
N/D	rs1279556849	-0.999	0.999	D	0.635	0.684	0.358948522604	gnomAD-4.0.0	1.59247E-06	None	None	None	None	I	None	5.66572E-05	0	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
N/A	0.9907	likely_pathogenic	0.9903	pathogenic	-0.415	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/C	0.9557	likely_pathogenic	0.9573	pathogenic	0.222	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
N/D	0.9822	likely_pathogenic	0.9836	pathogenic	-1.012	Destabilizing	0.999	D	0.635	neutral	D	0.548638104	None	None	I
N/E	0.9981	likely_pathogenic	0.9981	pathogenic	-1.028	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
N/F	0.9993	likely_pathogenic	0.9991	pathogenic	-0.908	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
N/G	0.9806	likely_pathogenic	0.9806	pathogenic	-0.587	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	I
N/H	0.9737	likely_pathogenic	0.971	pathogenic	-0.816	Destabilizing	1.0	D	0.752	deleterious	D	0.549905552	None	None	I
N/I	0.993	likely_pathogenic	0.992	pathogenic	-0.038	Destabilizing	1.0	D	0.711	prob.delet.	D	0.523660996	None	None	I
N/K	0.9987	likely_pathogenic	0.9985	pathogenic	0.059	Stabilizing	1.0	D	0.747	deleterious	D	0.549398573	None	None	I
N/L	0.9833	likely_pathogenic	0.9793	pathogenic	-0.038	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
N/M	0.9952	likely_pathogenic	0.9937	pathogenic	0.683	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
N/P	0.9952	likely_pathogenic	0.9947	pathogenic	-0.139	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/Q	0.9979	likely_pathogenic	0.9977	pathogenic	-0.763	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
N/R	0.997	likely_pathogenic	0.9965	pathogenic	0.226	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
N/S	0.672	likely_pathogenic	0.6902	pathogenic	-0.282	Destabilizing	0.999	D	0.6	neutral	N	0.501046836	None	None	I
N/T	0.9386	likely_pathogenic	0.9419	pathogenic	-0.174	Destabilizing	0.999	D	0.723	prob.delet.	D	0.530787339	None	None	I
N/V	0.9886	likely_pathogenic	0.9869	pathogenic	-0.139	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/W	0.9998	likely_pathogenic	0.9997	pathogenic	-0.86	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
N/Y	0.9931	likely_pathogenic	0.9918	pathogenic	-0.529	Destabilizing	1.0	D	0.729	prob.delet.	D	0.549905552	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.