TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33773	101542;101543;101544	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
N2AB	32132	96619;96620;96621	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
N2A	31205	93838;93839;93840	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
N2B	24708	74347;74348;74349	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
Novex-1	24833	74722;74723;74724	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
Novex-2	24900	74923;74924;74925	chr2:178535298;178535297;178535296	chr2:179400025;179400024;179400023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-132
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.3496
• 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
P/S	rs768248494	-1.002	0.979	N	0.714	0.38	0.313818047136	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
P/S	rs768248494	-1.002	0.979	N	0.714	0.38	0.313818047136	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85788E-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
P/A	0.2313	likely_benign	0.2314	benign	-1.528	Destabilizing	0.023	N	0.469	neutral	N	0.487545072	None	None	N
P/C	0.941	likely_pathogenic	0.9459	pathogenic	-0.965	Destabilizing	0.996	D	0.865	deleterious	None	None	None	None	N
P/D	0.9679	likely_pathogenic	0.9757	pathogenic	-1.339	Destabilizing	0.946	D	0.796	deleterious	None	None	None	None	N
P/E	0.8996	likely_pathogenic	0.9151	pathogenic	-1.38	Destabilizing	0.932	D	0.77	deleterious	None	None	None	None	N
P/F	0.9639	likely_pathogenic	0.9564	pathogenic	-1.332	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/G	0.8717	likely_pathogenic	0.9017	pathogenic	-1.799	Destabilizing	0.926	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.8576	likely_pathogenic	0.8549	pathogenic	-1.289	Destabilizing	1.0	D	0.843	deleterious	N	0.5217558	None	None	N
P/I	0.8907	likely_pathogenic	0.8982	pathogenic	-0.898	Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
P/K	0.9516	likely_pathogenic	0.9633	pathogenic	-1.188	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
P/L	0.7656	likely_pathogenic	0.764	pathogenic	-0.898	Destabilizing	0.997	D	0.771	deleterious	N	0.519727884	None	None	N
P/M	0.9231	likely_pathogenic	0.9266	pathogenic	-0.622	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/N	0.9519	likely_pathogenic	0.9633	pathogenic	-0.903	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	N
P/Q	0.8223	likely_pathogenic	0.8443	pathogenic	-1.159	Destabilizing	0.997	D	0.828	deleterious	None	None	None	None	N
P/R	0.8896	likely_pathogenic	0.9072	pathogenic	-0.595	Destabilizing	0.999	D	0.841	deleterious	N	0.506271665	None	None	N
P/S	0.6618	likely_pathogenic	0.6903	pathogenic	-1.393	Destabilizing	0.979	D	0.714	prob.delet.	N	0.494243796	None	None	N
P/T	0.673	likely_pathogenic	0.7112	pathogenic	-1.336	Destabilizing	0.976	D	0.721	prob.delet.	D	0.525514782	None	None	N
P/V	0.7715	likely_pathogenic	0.7866	pathogenic	-1.074	Destabilizing	0.975	D	0.733	prob.delet.	None	None	None	None	N
P/W	0.9855	likely_pathogenic	0.9835	pathogenic	-1.438	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Y	0.951	likely_pathogenic	0.9427	pathogenic	-1.182	Destabilizing	1.0	D	0.871	deleterious	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.