TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6228	18907;18908;18909	chr2:178729474;178729473;178729472	chr2:179594201;179594200;179594199
N2AB	5911	17956;17957;17958	chr2:178729474;178729473;178729472	chr2:179594201;179594200;179594199
N2A	4984	15175;15176;15177	chr2:178729474;178729473;178729472	chr2:179594201;179594200;179594199
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-46
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1478
• 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
F/S	rs1192303175	-2.888	0.991	N	0.705	0.495	0.784914850903	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
F/S	rs1192303175	-2.888	0.991	N	0.705	0.495	0.784914850903	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	2.28739E-05	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
F/A	0.7106	likely_pathogenic	0.7836	pathogenic	-2.708	Highly Destabilizing	0.953	D	0.634	neutral	None	None	None	None	N
F/C	0.4936	ambiguous	0.6279	pathogenic	-1.634	Destabilizing	0.999	D	0.675	prob.neutral	N	0.513609634	None	None	N
F/D	0.9617	likely_pathogenic	0.9695	pathogenic	-2.568	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
F/E	0.9632	likely_pathogenic	0.9716	pathogenic	-2.375	Highly Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
F/G	0.899	likely_pathogenic	0.9323	pathogenic	-3.139	Highly Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
F/H	0.8113	likely_pathogenic	0.8688	pathogenic	-1.598	Destabilizing	0.986	D	0.704	prob.neutral	None	None	None	None	N
F/I	0.3761	ambiguous	0.3751	ambiguous	-1.318	Destabilizing	0.982	D	0.664	neutral	N	0.501272413	None	None	N
F/K	0.9571	likely_pathogenic	0.9684	pathogenic	-1.719	Destabilizing	0.993	D	0.769	deleterious	None	None	None	None	N
F/L	0.8102	likely_pathogenic	0.8411	pathogenic	-1.318	Destabilizing	0.885	D	0.494	neutral	N	0.499192113	None	None	N
F/M	0.5724	likely_pathogenic	0.6325	pathogenic	-1.099	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
F/N	0.8755	likely_pathogenic	0.9135	pathogenic	-2.064	Highly Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
F/P	0.958	likely_pathogenic	0.9647	pathogenic	-1.789	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
F/Q	0.9226	likely_pathogenic	0.9485	pathogenic	-2.04	Highly Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
F/R	0.9058	likely_pathogenic	0.9294	pathogenic	-1.252	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
F/S	0.652	likely_pathogenic	0.742	pathogenic	-2.792	Highly Destabilizing	0.991	D	0.705	prob.neutral	N	0.48609763	None	None	N
F/T	0.7484	likely_pathogenic	0.8136	pathogenic	-2.491	Highly Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
F/V	0.3339	likely_benign	0.3637	ambiguous	-1.789	Destabilizing	0.939	D	0.65	neutral	N	0.499117542	None	None	N
F/W	0.5625	ambiguous	0.6214	pathogenic	-0.246	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
F/Y	0.2221	likely_benign	0.2733	benign	-0.611	Destabilizing	0.046	N	0.301	neutral	N	0.49047895	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.