TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18860	56803;56804;56805	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
N2AB	17219	51880;51881;51882	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
N2A	16292	49099;49100;49101	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
N2B	9795	29608;29609;29610	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
Novex-1	9920	29983;29984;29985	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
Novex-2	9987	30184;30185;30186	chr2:178599215;178599214;178599213	chr2:179463942;179463941;179463940
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-24
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1188
• 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
M/T	rs1384923019	None	0.979	N	0.685	0.33	0.643685692495	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/T	rs1384923019	None	0.979	N	0.685	0.33	0.643685692495	gnomAD-4.0.0	2.62433E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62988E-06	1.3832E-05	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
M/A	0.4397	ambiguous	0.3812	ambiguous	-2.524	Highly Destabilizing	0.963	D	0.677	prob.neutral	None	None	None	None	N
M/C	0.5557	ambiguous	0.4981	ambiguous	-2.357	Highly Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
M/D	0.9736	likely_pathogenic	0.9546	pathogenic	-2.414	Highly Destabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	N
M/E	0.7659	likely_pathogenic	0.6689	pathogenic	-2.258	Highly Destabilizing	0.969	D	0.641	neutral	None	None	None	None	N
M/F	0.4653	ambiguous	0.3622	ambiguous	-1.02	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
M/G	0.7681	likely_pathogenic	0.675	pathogenic	-2.908	Highly Destabilizing	0.984	D	0.657	neutral	None	None	None	None	N
M/H	0.5626	ambiguous	0.477	ambiguous	-2.348	Highly Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
M/I	0.7102	likely_pathogenic	0.5773	pathogenic	-1.433	Destabilizing	0.993	D	0.743	deleterious	N	0.453120601	None	None	N
M/K	0.1919	likely_benign	0.1424	benign	-1.827	Destabilizing	0.921	D	0.688	prob.neutral	N	0.444095686	None	None	N
M/L	0.2839	likely_benign	0.2283	benign	-1.433	Destabilizing	0.895	D	0.521	neutral	N	0.47234108	None	None	N
M/N	0.7759	likely_pathogenic	0.6959	pathogenic	-1.96	Destabilizing	0.995	D	0.684	prob.neutral	None	None	None	None	N
M/P	0.9964	likely_pathogenic	0.994	pathogenic	-1.78	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
M/Q	0.2481	likely_benign	0.2072	benign	-1.822	Destabilizing	0.969	D	0.715	prob.delet.	None	None	None	None	N
M/R	0.1677	likely_benign	0.1329	benign	-1.604	Destabilizing	0.068	N	0.475	neutral	N	0.399208759	None	None	N
M/S	0.4016	ambiguous	0.3577	ambiguous	-2.493	Highly Destabilizing	0.984	D	0.685	prob.neutral	None	None	None	None	N
M/T	0.2495	likely_benign	0.2071	benign	-2.245	Highly Destabilizing	0.979	D	0.685	prob.neutral	N	0.453773962	None	None	N
M/V	0.1947	likely_benign	0.1631	benign	-1.78	Destabilizing	0.951	D	0.749	deleterious	N	0.446405273	None	None	N
M/W	0.7741	likely_pathogenic	0.6717	pathogenic	-1.271	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
M/Y	0.714	likely_pathogenic	0.5972	pathogenic	-1.327	Destabilizing	0.999	D	0.719	prob.delet.	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.