TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18888	56887;56888;56889	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
N2AB	17247	51964;51965;51966	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
N2A	16320	49183;49184;49185	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
N2B	9823	29692;29693;29694	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
Novex-1	9948	30067;30068;30069	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
Novex-2	10015	30268;30269;30270	chr2:178599048;178599047;178599046	chr2:179463775;179463774;179463773
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-25
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.1081
• 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
P/S	rs755206756	-2.841	0.801	D	0.776	0.524	0.466991082792	gnomAD-2.1.1	1.44E-05	None	None	None	None	N	None	0	1.20077E-04	None	0	0	None	0	None	0	0	0
P/S	rs755206756	-2.841	0.801	D	0.776	0.524	0.466991082792	gnomAD-4.0.0	1.41814E-06	None	None	None	None	N	None	0	5.72377E-05	None	0	0	None	0	0	0	0	0
P/T	None	None	0.801	D	0.781	0.532	0.497021753114	gnomAD-4.0.0	7.09071E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.72182E-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
P/A	0.4192	ambiguous	0.4257	ambiguous	-2.052	Highly Destabilizing	0.454	N	0.685	prob.neutral	D	0.543321501	None	None	N
P/C	0.566	likely_pathogenic	0.552	ambiguous	-1.822	Destabilizing	0.002	N	0.657	neutral	None	None	None	None	N
P/D	0.9966	likely_pathogenic	0.997	pathogenic	-2.968	Highly Destabilizing	0.971	D	0.817	deleterious	None	None	None	None	N
P/E	0.9934	likely_pathogenic	0.9936	pathogenic	-2.853	Highly Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
P/F	0.9962	likely_pathogenic	0.9971	pathogenic	-1.328	Destabilizing	0.991	D	0.871	deleterious	None	None	None	None	N
P/G	0.9372	likely_pathogenic	0.9411	pathogenic	-2.491	Highly Destabilizing	0.915	D	0.825	deleterious	None	None	None	None	N
P/H	0.9898	likely_pathogenic	0.9927	pathogenic	-2.136	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
P/I	0.9341	likely_pathogenic	0.918	pathogenic	-0.864	Destabilizing	0.949	D	0.851	deleterious	None	None	None	None	N
P/K	0.9957	likely_pathogenic	0.9958	pathogenic	-1.776	Destabilizing	0.971	D	0.817	deleterious	None	None	None	None	N
P/L	0.8354	likely_pathogenic	0.85	pathogenic	-0.864	Destabilizing	0.669	D	0.813	deleterious	D	0.549144398	None	None	N
P/M	0.9519	likely_pathogenic	0.9511	pathogenic	-0.911	Destabilizing	0.991	D	0.859	deleterious	None	None	None	None	N
P/N	0.9924	likely_pathogenic	0.9925	pathogenic	-1.915	Destabilizing	0.991	D	0.844	deleterious	None	None	None	None	N
P/Q	0.9823	likely_pathogenic	0.9848	pathogenic	-1.949	Destabilizing	0.989	D	0.808	deleterious	D	0.562439714	None	None	N
P/R	0.9845	likely_pathogenic	0.9862	pathogenic	-1.387	Destabilizing	0.989	D	0.845	deleterious	D	0.561932735	None	None	N
P/S	0.8753	likely_pathogenic	0.8896	pathogenic	-2.417	Highly Destabilizing	0.801	D	0.776	deleterious	D	0.550665335	None	None	N
P/T	0.7921	likely_pathogenic	0.7554	pathogenic	-2.185	Highly Destabilizing	0.801	D	0.781	deleterious	D	0.543321501	None	None	N
P/V	0.7578	likely_pathogenic	0.7117	pathogenic	-1.232	Destabilizing	0.842	D	0.821	deleterious	None	None	None	None	N
P/W	0.9987	likely_pathogenic	0.9992	pathogenic	-1.756	Destabilizing	0.998	D	0.86	deleterious	None	None	None	None	N
P/Y	0.9976	likely_pathogenic	0.9983	pathogenic	-1.452	Destabilizing	0.991	D	0.871	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.