TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23158	69697;69698;69699	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
N2AB	21517	64774;64775;64776	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
N2A	20590	61993;61994;61995	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
N2B	14093	42502;42503;42504	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
Novex-1	14218	42877;42878;42879	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
Novex-2	14285	43078;43079;43080	chr2:178576772;178576771;178576770	chr2:179441499;179441498;179441497
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: Fn3-56
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1387
• 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	None	N	0.165	0.034	0.207176502487	gnomAD-4.0.0	1.36867E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79916E-06	0	0
V/L	rs781570281	-0.285	0.009	N	0.423	0.066	0.124217242631	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
V/L	rs781570281	-0.285	0.009	N	0.423	0.066	0.124217242631	gnomAD-4.0.0	1.36867E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.74574E-05	0	0	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	0.8374	likely_pathogenic	0.8249	pathogenic	-2.081	Highly Destabilizing	0.104	N	0.671	neutral	N	0.500112237	None	None	N
V/C	0.9452	likely_pathogenic	0.9366	pathogenic	-1.803	Destabilizing	0.968	D	0.719	prob.delet.	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9976	pathogenic	-2.82	Highly Destabilizing	0.667	D	0.886	deleterious	N	0.512647085	None	None	N
V/E	0.9941	likely_pathogenic	0.9923	pathogenic	-2.543	Highly Destabilizing	0.726	D	0.845	deleterious	None	None	None	None	N
V/F	0.7186	likely_pathogenic	0.663	pathogenic	-1.187	Destabilizing	0.497	N	0.728	prob.delet.	N	0.477146137	None	None	N
V/G	0.96	likely_pathogenic	0.9527	pathogenic	-2.679	Highly Destabilizing	0.667	D	0.868	deleterious	N	0.512393596	None	None	N
V/H	0.9972	likely_pathogenic	0.9962	pathogenic	-2.597	Highly Destabilizing	0.968	D	0.867	deleterious	None	None	None	None	N
V/I	0.0668	likely_benign	0.0629	benign	-0.382	Destabilizing	None	N	0.165	neutral	N	0.418893385	None	None	N
V/K	0.9948	likely_pathogenic	0.9933	pathogenic	-1.715	Destabilizing	0.726	D	0.845	deleterious	None	None	None	None	N
V/L	0.217	likely_benign	0.1755	benign	-0.382	Destabilizing	0.009	N	0.423	neutral	N	0.373205875	None	None	N
V/M	0.4589	ambiguous	0.425	ambiguous	-0.655	Destabilizing	0.567	D	0.661	neutral	None	None	None	None	N
V/N	0.9933	likely_pathogenic	0.9915	pathogenic	-2.207	Highly Destabilizing	0.89	D	0.88	deleterious	None	None	None	None	N
V/P	0.9943	likely_pathogenic	0.9909	pathogenic	-0.923	Destabilizing	0.89	D	0.846	deleterious	None	None	None	None	N
V/Q	0.9915	likely_pathogenic	0.9892	pathogenic	-1.926	Destabilizing	0.89	D	0.87	deleterious	None	None	None	None	N
V/R	0.9893	likely_pathogenic	0.9866	pathogenic	-1.755	Destabilizing	0.726	D	0.885	deleterious	None	None	None	None	N
V/S	0.9736	likely_pathogenic	0.9712	pathogenic	-2.826	Highly Destabilizing	0.726	D	0.809	deleterious	None	None	None	None	N
V/T	0.925	likely_pathogenic	0.9211	pathogenic	-2.386	Highly Destabilizing	0.272	N	0.651	neutral	None	None	None	None	N
V/W	0.9956	likely_pathogenic	0.993	pathogenic	-1.767	Destabilizing	0.968	D	0.832	deleterious	None	None	None	None	N
V/Y	0.9815	likely_pathogenic	0.974	pathogenic	-1.359	Destabilizing	0.726	D	0.723	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.