TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23346	70261;70262;70263	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
N2AB	21705	65338;65339;65340	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
N2A	20778	62557;62558;62559	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
N2B	14281	43066;43067;43068	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
Novex-1	14406	43441;43442;43443	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
Novex-2	14473	43642;43643;43644	chr2:178576096;178576095;178576094	chr2:179440823;179440822;179440821
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: Ig-129
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5332
• 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
L/I	None	None	0.999	N	0.405	0.247	0.409124616982	gnomAD-4.0.0	6.84332E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99593E-07	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	0.9056	likely_pathogenic	0.9115	pathogenic	-1.411	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
L/C	0.9568	likely_pathogenic	0.9584	pathogenic	-0.918	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
L/D	0.9918	likely_pathogenic	0.9929	pathogenic	-0.796	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
L/E	0.9631	likely_pathogenic	0.9684	pathogenic	-0.81	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
L/F	0.6855	likely_pathogenic	0.6906	pathogenic	-0.974	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
L/G	0.976	likely_pathogenic	0.9764	pathogenic	-1.711	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
L/H	0.9627	likely_pathogenic	0.9646	pathogenic	-0.915	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
L/I	0.2663	likely_benign	0.2827	benign	-0.675	Destabilizing	0.999	D	0.405	neutral	N	0.492391507	None	None	I
L/K	0.9355	likely_pathogenic	0.937	pathogenic	-1.019	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/M	0.2783	likely_benign	0.2975	benign	-0.592	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	I
L/N	0.9715	likely_pathogenic	0.9748	pathogenic	-0.799	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
L/P	0.9106	likely_pathogenic	0.9066	pathogenic	-0.887	Destabilizing	1.0	D	0.757	deleterious	N	0.513626542	None	None	I
L/Q	0.9252	likely_pathogenic	0.9291	pathogenic	-0.97	Destabilizing	1.0	D	0.733	prob.delet.	D	0.5259079	None	None	I
L/R	0.9254	likely_pathogenic	0.9289	pathogenic	-0.435	Destabilizing	1.0	D	0.739	prob.delet.	N	0.51438701	None	None	I
L/S	0.9804	likely_pathogenic	0.9824	pathogenic	-1.38	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/T	0.8766	likely_pathogenic	0.8831	pathogenic	-1.274	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
L/V	0.3789	ambiguous	0.3931	ambiguous	-0.887	Destabilizing	0.999	D	0.456	neutral	N	0.502480365	None	None	I
L/W	0.8376	likely_pathogenic	0.8552	pathogenic	-1.022	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
L/Y	0.9234	likely_pathogenic	0.9263	pathogenic	-0.809	Destabilizing	1.0	D	0.715	prob.delet.	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.