TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29678	89257;89258;89259	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
N2AB	28037	84334;84335;84336	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
N2A	27110	81553;81554;81555	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
N2B	20613	62062;62063;62064	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
Novex-1	20738	62437;62438;62439	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
Novex-2	20805	62638;62639;62640	chr2:178554079;178554078;178554077	chr2:179418806;179418805;179418804
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-104
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.1013
• 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
L/P	None	None	1.0	N	0.735	0.572	0.706817979235	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85804E-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
L/A	0.162	likely_benign	0.178	benign	-0.511	Destabilizing	0.999	D	0.64	neutral	None	None	None	None	N
L/C	0.5096	ambiguous	0.5371	ambiguous	-0.968	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
L/D	0.7184	likely_pathogenic	0.7538	pathogenic	-0.043	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
L/E	0.4742	ambiguous	0.5045	ambiguous	-0.124	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
L/F	0.1599	likely_benign	0.1815	benign	-0.675	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
L/G	0.4161	ambiguous	0.4584	ambiguous	-0.577	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/H	0.2623	likely_benign	0.2886	benign	-0.052	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
L/I	0.0978	likely_benign	0.0987	benign	-0.444	Destabilizing	0.999	D	0.556	neutral	N	0.484849018	None	None	N
L/K	0.3652	ambiguous	0.3695	ambiguous	-0.388	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/M	0.1141	likely_benign	0.1144	benign	-0.707	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
L/N	0.343	ambiguous	0.3637	ambiguous	-0.304	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
L/P	0.1699	likely_benign	0.1927	benign	-0.443	Destabilizing	1.0	D	0.735	prob.delet.	N	0.491081557	None	None	N
L/Q	0.1762	likely_benign	0.1793	benign	-0.417	Destabilizing	1.0	D	0.722	prob.delet.	N	0.458873138	None	None	N
L/R	0.2497	likely_benign	0.2661	benign	-0.038	Destabilizing	1.0	D	0.731	prob.delet.	N	0.476864253	None	None	N
L/S	0.2063	likely_benign	0.2326	benign	-0.711	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
L/T	0.1438	likely_benign	0.1534	benign	-0.698	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
L/V	0.0916	likely_benign	0.0933	benign	-0.443	Destabilizing	0.999	D	0.584	neutral	N	0.464396388	None	None	N
L/W	0.2889	likely_benign	0.3331	benign	-0.684	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
L/Y	0.3847	ambiguous	0.4218	ambiguous	-0.487	Destabilizing	1.0	D	0.699	prob.neutral	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.