TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5300	16123;16124;16125	chr2:178733395;178733394;178733393	chr2:179598122;179598121;179598120
N2AB	4983	15172;15173;15174	chr2:178733395;178733394;178733393	chr2:179598122;179598121;179598120
N2A	4056	12391;12392;12393	chr2:178733395;178733394;178733393	chr2:179598122;179598121;179598120
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-36
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.3502
• 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/H	rs1248409979	None	1.0	N	0.549	0.429	0.598413393357	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
P/S	rs1436998315	-0.65	0.925	N	0.376	0.274	0.306053231325	gnomAD-4.0.0	6.8421E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65662E-05
P/T	None	None	0.961	N	0.403	0.288	0.483082108137	gnomAD-4.0.0	1.36842E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79896E-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	0.0909	likely_benign	0.0882	benign	-0.688	Destabilizing	0.248	N	0.209	neutral	N	0.510289035	None	None	N
P/C	0.5572	ambiguous	0.5416	ambiguous	-0.647	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
P/D	0.5384	ambiguous	0.5154	ambiguous	-0.424	Destabilizing	0.942	D	0.373	neutral	None	None	None	None	N
P/E	0.2564	likely_benign	0.2377	benign	-0.476	Destabilizing	0.155	N	0.186	neutral	None	None	None	None	N
P/F	0.4579	ambiguous	0.4544	ambiguous	-0.627	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
P/G	0.3999	ambiguous	0.4075	ambiguous	-0.887	Destabilizing	0.97	D	0.435	neutral	None	None	None	None	N
P/H	0.2178	likely_benign	0.2185	benign	-0.266	Destabilizing	1.0	D	0.549	neutral	N	0.509599753	None	None	N
P/I	0.2428	likely_benign	0.2287	benign	-0.28	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
P/K	0.3023	likely_benign	0.2872	benign	-0.601	Destabilizing	0.97	D	0.357	neutral	None	None	None	None	N
P/L	0.1007	likely_benign	0.1	benign	-0.28	Destabilizing	0.961	D	0.467	neutral	N	0.49240079	None	None	N
P/M	0.2591	likely_benign	0.2514	benign	-0.462	Destabilizing	1.0	D	0.558	neutral	None	None	None	None	N
P/N	0.385	ambiguous	0.3715	ambiguous	-0.419	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
P/Q	0.1392	likely_benign	0.1363	benign	-0.587	Destabilizing	0.991	D	0.415	neutral	None	None	None	None	N
P/R	0.2137	likely_benign	0.2088	benign	-0.099	Destabilizing	0.989	D	0.487	neutral	N	0.509461795	None	None	N
P/S	0.1591	likely_benign	0.1579	benign	-0.827	Destabilizing	0.925	D	0.376	neutral	N	0.507929336	None	None	N
P/T	0.1279	likely_benign	0.1242	benign	-0.771	Destabilizing	0.961	D	0.403	neutral	N	0.512328239	None	None	N
P/V	0.1782	likely_benign	0.1717	benign	-0.382	Destabilizing	0.97	D	0.457	neutral	None	None	None	None	N
P/W	0.6505	likely_pathogenic	0.6566	pathogenic	-0.744	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
P/Y	0.441	ambiguous	0.4363	ambiguous	-0.45	Destabilizing	0.999	D	0.583	neutral	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.