TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4866	14821;14822;14823	chr2:178735850;178735849;178735848	chr2:179600577;179600576;179600575
N2AB	4549	13870;13871;13872	chr2:178735850;178735849;178735848	chr2:179600577;179600576;179600575
N2A	3622	11089;11090;11091	chr2:178735850;178735849;178735848	chr2:179600577;179600576;179600575
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-31
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1221
• 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
S/F	rs1226951123	-0.701	0.642	N	0.729	0.272	0.532020707701	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
S/F	rs1226951123	-0.701	0.642	N	0.729	0.272	0.532020707701	gnomAD-4.0.0	3.18256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71608E-06	0	0
S/Y	None	None	0.975	N	0.727	0.307	0.548779645056	gnomAD-4.0.0	1.59128E-06	None	None	None	None	N	None	0	2.28686E-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
S/A	0.1109	likely_benign	0.0957	benign	-0.897	Destabilizing	0.001	N	0.143	neutral	N	0.505837832	None	None	N
S/C	0.1354	likely_benign	0.1157	benign	-0.718	Destabilizing	0.975	D	0.669	neutral	N	0.509506755	None	None	N
S/D	0.7629	likely_pathogenic	0.6894	pathogenic	-1.711	Destabilizing	0.704	D	0.569	neutral	None	None	None	None	N
S/E	0.7612	likely_pathogenic	0.7156	pathogenic	-1.494	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	N
S/F	0.2309	likely_benign	0.1855	benign	-0.683	Destabilizing	0.642	D	0.729	prob.delet.	N	0.516122503	None	None	N
S/G	0.1879	likely_benign	0.1419	benign	-1.293	Destabilizing	0.329	N	0.455	neutral	None	None	None	None	N
S/H	0.469	ambiguous	0.4085	ambiguous	-1.59	Destabilizing	0.981	D	0.665	neutral	None	None	None	None	N
S/I	0.2002	likely_benign	0.1628	benign	0.116	Stabilizing	0.329	N	0.677	prob.neutral	None	None	None	None	N
S/K	0.8685	likely_pathogenic	0.8196	pathogenic	-0.216	Destabilizing	0.495	N	0.481	neutral	None	None	None	None	N
S/L	0.1237	likely_benign	0.1018	benign	0.116	Stabilizing	0.001	N	0.485	neutral	None	None	None	None	N
S/M	0.3065	likely_benign	0.2497	benign	-0.07	Destabilizing	0.893	D	0.676	prob.neutral	None	None	None	None	N
S/N	0.3047	likely_benign	0.2238	benign	-1.008	Destabilizing	0.704	D	0.551	neutral	None	None	None	None	N
S/P	0.9689	likely_pathogenic	0.9548	pathogenic	-0.188	Destabilizing	0.784	D	0.69	prob.neutral	D	0.650645063	None	None	N
S/Q	0.6638	likely_pathogenic	0.6137	pathogenic	-0.714	Destabilizing	0.828	D	0.611	neutral	None	None	None	None	N
S/R	0.7279	likely_pathogenic	0.6649	pathogenic	-0.658	Destabilizing	0.704	D	0.695	prob.neutral	None	None	None	None	N
S/T	0.0934	likely_benign	0.0803	benign	-0.62	Destabilizing	0.01	N	0.224	neutral	N	0.342185129	None	None	N
S/V	0.2345	likely_benign	0.1903	benign	-0.188	Destabilizing	0.013	N	0.524	neutral	None	None	None	None	N
S/W	0.406	ambiguous	0.3726	ambiguous	-0.998	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
S/Y	0.2125	likely_benign	0.1858	benign	-0.53	Destabilizing	0.975	D	0.727	prob.delet.	N	0.504349562	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.