TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26323	79192;79193;79194	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
N2AB	24682	74269;74270;74271	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
N2A	23755	71488;71489;71490	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
N2B	17258	51997;51998;51999	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
Novex-1	17383	52372;52373;52374	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
Novex-2	17450	52573;52574;52575	chr2:178567165;178567164;178567163	chr2:179431892;179431891;179431890
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-79
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1768
• 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
V/G	None	None	0.642	N	0.713	0.367	0.767911445349	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
V/I	None	None	0.001	N	0.308	0.033	0.36893422563	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
V/A	0.4494	ambiguous	0.491	ambiguous	-2.281	Highly Destabilizing	0.003	N	0.484	neutral	N	0.475532613	None	None	N
V/C	0.7866	likely_pathogenic	0.7868	pathogenic	-1.73	Destabilizing	0.973	D	0.711	prob.delet.	None	None	None	None	N
V/D	0.893	likely_pathogenic	0.889	pathogenic	-3.175	Highly Destabilizing	0.879	D	0.767	deleterious	N	0.477089549	None	None	N
V/E	0.7	likely_pathogenic	0.7362	pathogenic	-3.003	Highly Destabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	N
V/F	0.3497	ambiguous	0.3306	benign	-1.351	Destabilizing	0.782	D	0.709	prob.delet.	N	0.512323621	None	None	N
V/G	0.703	likely_pathogenic	0.7538	pathogenic	-2.739	Highly Destabilizing	0.642	D	0.713	prob.delet.	N	0.496714742	None	None	N
V/H	0.8091	likely_pathogenic	0.7907	pathogenic	-2.479	Highly Destabilizing	0.991	D	0.748	deleterious	None	None	None	None	N
V/I	0.0601	likely_benign	0.056	benign	-1.004	Destabilizing	0.001	N	0.308	neutral	N	0.403329286	None	None	N
V/K	0.6605	likely_pathogenic	0.6896	pathogenic	-2.02	Highly Destabilizing	0.826	D	0.689	prob.neutral	None	None	None	None	N
V/L	0.2171	likely_benign	0.2015	benign	-1.004	Destabilizing	0.068	N	0.532	neutral	N	0.502029269	None	None	N
V/M	0.1726	likely_benign	0.1832	benign	-0.97	Destabilizing	0.826	D	0.677	prob.neutral	None	None	None	None	N
V/N	0.6836	likely_pathogenic	0.6633	pathogenic	-2.253	Highly Destabilizing	0.906	D	0.772	deleterious	None	None	None	None	N
V/P	0.9915	likely_pathogenic	0.9888	pathogenic	-1.407	Destabilizing	0.906	D	0.719	prob.delet.	None	None	None	None	N
V/Q	0.6182	likely_pathogenic	0.6632	pathogenic	-2.164	Highly Destabilizing	0.906	D	0.731	prob.delet.	None	None	None	None	N
V/R	0.5697	likely_pathogenic	0.5857	pathogenic	-1.673	Destabilizing	0.826	D	0.768	deleterious	None	None	None	None	N
V/S	0.5267	ambiguous	0.5539	ambiguous	-2.745	Highly Destabilizing	0.704	D	0.677	prob.neutral	None	None	None	None	N
V/T	0.2662	likely_benign	0.2903	benign	-2.468	Highly Destabilizing	0.575	D	0.639	neutral	None	None	None	None	N
V/W	0.9147	likely_pathogenic	0.8941	pathogenic	-1.929	Destabilizing	0.991	D	0.705	prob.neutral	None	None	None	None	N
V/Y	0.7604	likely_pathogenic	0.7277	pathogenic	-1.633	Destabilizing	0.906	D	0.72	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.