TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17399	52420;52421;52422	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
N2AB	15758	47497;47498;47499	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
N2A	14831	44716;44717;44718	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
N2B	8334	25225;25226;25227	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
Novex-1	8459	25600;25601;25602	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
Novex-2	8526	25801;25802;25803	chr2:178608816;178608815;178608814	chr2:179473543;179473542;179473541
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-14
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.1357
• 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
S/N	rs1364503531	-0.708	0.999	N	0.707	0.313	0.248417906384	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/N	rs1364503531	-0.708	0.999	N	0.707	0.313	0.248417906384	gnomAD-4.0.0	3.18816E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72384E-06	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
S/A	0.156	likely_benign	0.1423	benign	-0.883	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	I
S/C	0.1303	likely_benign	0.1245	benign	-0.587	Destabilizing	1.0	D	0.829	deleterious	N	0.476981553	None	None	I
S/D	0.9367	likely_pathogenic	0.9418	pathogenic	-0.326	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	I
S/E	0.9445	likely_pathogenic	0.9518	pathogenic	-0.317	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	I
S/F	0.7585	likely_pathogenic	0.7328	pathogenic	-1.046	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
S/G	0.2605	likely_benign	0.2601	benign	-1.139	Destabilizing	0.999	D	0.595	neutral	N	0.463247574	None	None	I
S/H	0.8566	likely_pathogenic	0.8573	pathogenic	-1.569	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
S/I	0.707	likely_pathogenic	0.7046	pathogenic	-0.301	Destabilizing	1.0	D	0.828	deleterious	N	0.503528824	None	None	I
S/K	0.9829	likely_pathogenic	0.9856	pathogenic	-0.703	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
S/L	0.4213	ambiguous	0.3929	ambiguous	-0.301	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
S/M	0.4805	ambiguous	0.4718	ambiguous	0.023	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
S/N	0.6305	likely_pathogenic	0.6083	pathogenic	-0.694	Destabilizing	0.999	D	0.707	prob.neutral	N	0.493324608	None	None	I
S/P	0.9913	likely_pathogenic	0.9911	pathogenic	-0.462	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
S/Q	0.8995	likely_pathogenic	0.9054	pathogenic	-0.85	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
S/R	0.969	likely_pathogenic	0.9719	pathogenic	-0.604	Destabilizing	1.0	D	0.825	deleterious	N	0.494094622	None	None	I
S/T	0.2501	likely_benign	0.2407	benign	-0.724	Destabilizing	0.999	D	0.615	neutral	N	0.479246051	None	None	I
S/V	0.5758	likely_pathogenic	0.5702	pathogenic	-0.462	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
S/W	0.8528	likely_pathogenic	0.8542	pathogenic	-0.988	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
S/Y	0.7346	likely_pathogenic	0.7282	pathogenic	-0.733	Destabilizing	1.0	D	0.848	deleterious	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.