TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23131	69616;69617;69618	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
N2AB	21490	64693;64694;64695	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
N2A	20563	61912;61913;61914	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
N2B	14066	42421;42422;42423	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
Novex-1	14191	42796;42797;42798	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
Novex-2	14258	42997;42998;42999	chr2:178576944;178576943;178576942	chr2:179441671;179441670;179441669
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-55
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.1924
• 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/I	None	None	0.049	N	0.289	0.076	0.39724302092	gnomAD-4.0.0	2.74301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70259E-06	1.16618E-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
V/A	0.3218	likely_benign	0.3049	benign	-1.703	Destabilizing	0.792	D	0.513	neutral	N	0.488085866	None	None	N
V/C	0.7574	likely_pathogenic	0.7569	pathogenic	-1.092	Destabilizing	0.998	D	0.727	deleterious	None	None	None	None	N
V/D	0.9004	likely_pathogenic	0.9066	pathogenic	-1.825	Destabilizing	0.988	D	0.897	deleterious	D	0.546072389	None	None	N
V/E	0.68	likely_pathogenic	0.672	pathogenic	-1.708	Destabilizing	0.973	D	0.837	deleterious	None	None	None	None	N
V/F	0.3276	likely_benign	0.3294	benign	-1.071	Destabilizing	0.931	D	0.759	deleterious	N	0.514672818	None	None	N
V/G	0.5157	ambiguous	0.5267	ambiguous	-2.124	Highly Destabilizing	0.964	D	0.885	deleterious	D	0.545818899	None	None	N
V/H	0.8585	likely_pathogenic	0.8603	pathogenic	-1.564	Destabilizing	0.998	D	0.836	deleterious	None	None	None	None	N
V/I	0.0846	likely_benign	0.0804	benign	-0.589	Destabilizing	0.049	N	0.289	neutral	N	0.492343498	None	None	N
V/K	0.6563	likely_pathogenic	0.6609	pathogenic	-1.497	Destabilizing	0.947	D	0.825	deleterious	None	None	None	None	N
V/L	0.2568	likely_benign	0.2217	benign	-0.589	Destabilizing	0.214	N	0.435	neutral	N	0.502262874	None	None	N
V/M	0.1835	likely_benign	0.1624	benign	-0.478	Destabilizing	0.511	D	0.479	neutral	None	None	None	None	N
V/N	0.7913	likely_pathogenic	0.7911	pathogenic	-1.546	Destabilizing	0.973	D	0.885	deleterious	None	None	None	None	N
V/P	0.9819	likely_pathogenic	0.9835	pathogenic	-0.929	Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
V/Q	0.5848	likely_pathogenic	0.5729	pathogenic	-1.559	Destabilizing	0.973	D	0.811	deleterious	None	None	None	None	N
V/R	0.6031	likely_pathogenic	0.6168	pathogenic	-1.084	Destabilizing	0.973	D	0.889	deleterious	None	None	None	None	N
V/S	0.5546	ambiguous	0.5574	ambiguous	-2.108	Highly Destabilizing	0.947	D	0.769	deleterious	None	None	None	None	N
V/T	0.2952	likely_benign	0.2935	benign	-1.862	Destabilizing	0.835	D	0.562	neutral	None	None	None	None	N
V/W	0.9366	likely_pathogenic	0.9346	pathogenic	-1.396	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
V/Y	0.8106	likely_pathogenic	0.8191	pathogenic	-1.047	Destabilizing	0.973	D	0.712	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.