TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5610	17053;17054;17055	chr2:178732141;178732140;178732139	chr2:179596868;179596867;179596866
N2AB	5293	16102;16103;16104	chr2:178732141;178732140;178732139	chr2:179596868;179596867;179596866
N2A	4366	13321;13322;13323	chr2:178732141;178732140;178732139	chr2:179596868;179596867;179596866
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-39
• Domain position: 68
• Structural Position: 149
• Q(SASA): 0.2486
• 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
D/N	None	None	0.999	D	0.789	0.586	0.718595846919	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85855E-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
D/A	0.4707	ambiguous	0.5135	ambiguous	-0.202	Destabilizing	0.999	D	0.83	deleterious	D	0.626692306	None	None	N
D/C	0.8318	likely_pathogenic	0.854	pathogenic	-0.064	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
D/E	0.4236	ambiguous	0.4285	ambiguous	-0.766	Destabilizing	0.767	D	0.397	neutral	D	0.587174312	None	None	N
D/F	0.8177	likely_pathogenic	0.8344	pathogenic	0.341	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
D/G	0.4615	ambiguous	0.5148	ambiguous	-0.622	Destabilizing	0.998	D	0.777	deleterious	D	0.664272619	None	None	N
D/H	0.5559	ambiguous	0.5812	pathogenic	-0.092	Destabilizing	1.0	D	0.819	deleterious	D	0.592735546	None	None	N
D/I	0.736	likely_pathogenic	0.7653	pathogenic	0.919	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
D/K	0.8339	likely_pathogenic	0.8475	pathogenic	-0.194	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
D/L	0.7752	likely_pathogenic	0.795	pathogenic	0.919	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/M	0.853	likely_pathogenic	0.873	pathogenic	1.385	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
D/N	0.2447	likely_benign	0.2641	benign	-0.879	Destabilizing	0.999	D	0.789	deleterious	D	0.592806985	None	None	N
D/P	0.9751	likely_pathogenic	0.9823	pathogenic	0.573	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/Q	0.7287	likely_pathogenic	0.7574	pathogenic	-0.612	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
D/R	0.8715	likely_pathogenic	0.8904	pathogenic	-0.125	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
D/S	0.3775	ambiguous	0.4149	ambiguous	-1.118	Destabilizing	0.997	D	0.701	prob.neutral	None	None	None	None	N
D/T	0.6525	likely_pathogenic	0.6889	pathogenic	-0.745	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/V	0.5379	ambiguous	0.5715	pathogenic	0.573	Stabilizing	0.999	D	0.866	deleterious	D	0.639138116	None	None	N
D/W	0.9608	likely_pathogenic	0.9678	pathogenic	0.473	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/Y	0.3952	ambiguous	0.406	ambiguous	0.589	Stabilizing	1.0	D	0.875	deleterious	D	0.638936311	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.