TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21298	64117;64118;64119	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
N2AB	19657	59194;59195;59196	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
N2A	18730	56413;56414;56415	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
N2B	12233	36922;36923;36924	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
Novex-1	12358	37297;37298;37299	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
Novex-2	12425	37498;37499;37500	chr2:178587319;178587318;178587317	chr2:179452046;179452045;179452044
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-42
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3024
• 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
V/M	rs1236931080	-0.511	0.997	N	0.717	0.379	0.614204031915	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
V/M	rs1236931080	-0.511	0.997	N	0.717	0.379	0.614204031915	gnomAD-4.0.0	2.73829E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69918E-06	0	1.65799E-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
V/A	0.8397	likely_pathogenic	0.8746	pathogenic	-1.953	Destabilizing	0.948	D	0.619	neutral	N	0.480411367	None	None	N
V/C	0.9249	likely_pathogenic	0.945	pathogenic	-1.388	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/D	0.9907	likely_pathogenic	0.9922	pathogenic	-2.514	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/E	0.9725	likely_pathogenic	0.9767	pathogenic	-2.438	Highly Destabilizing	0.999	D	0.792	deleterious	N	0.506366435	None	None	N
V/F	0.8394	likely_pathogenic	0.8708	pathogenic	-1.429	Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
V/G	0.8983	likely_pathogenic	0.9157	pathogenic	-2.357	Highly Destabilizing	0.999	D	0.791	deleterious	N	0.506112945	None	None	N
V/H	0.9911	likely_pathogenic	0.994	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
V/I	0.074	likely_benign	0.0764	benign	-0.89	Destabilizing	0.246	N	0.221	neutral	None	None	None	None	N
V/K	0.9822	likely_pathogenic	0.9847	pathogenic	-1.732	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/L	0.3876	ambiguous	0.4727	ambiguous	-0.89	Destabilizing	0.9	D	0.439	neutral	N	0.492564424	None	None	N
V/M	0.5112	ambiguous	0.5816	pathogenic	-0.665	Destabilizing	0.997	D	0.717	prob.delet.	N	0.505352476	None	None	N
V/N	0.9514	likely_pathogenic	0.9621	pathogenic	-1.706	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/P	0.7996	likely_pathogenic	0.8354	pathogenic	-1.213	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/Q	0.9735	likely_pathogenic	0.9796	pathogenic	-1.793	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/R	0.9771	likely_pathogenic	0.98	pathogenic	-1.252	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
V/S	0.9384	likely_pathogenic	0.9514	pathogenic	-2.2	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
V/T	0.8357	likely_pathogenic	0.8687	pathogenic	-2.014	Highly Destabilizing	0.992	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.9944	likely_pathogenic	0.9965	pathogenic	-1.82	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
V/Y	0.9737	likely_pathogenic	0.9806	pathogenic	-1.506	Destabilizing	0.999	D	0.745	deleterious	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.