TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6320	19183;19184;19185	chr2:178729080;178729079;178729078	chr2:179593807;179593806;179593805
N2AB	6003	18232;18233;18234	chr2:178729080;178729079;178729078	chr2:179593807;179593806;179593805
N2A	5076	15451;15452;15453	chr2:178729080;178729079;178729078	chr2:179593807;179593806;179593805
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: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-47
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7481
• Predicted PPI site: I

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	rs886246785	None	1.0	D	0.533	0.463	0.590966807702	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
P/H	rs886246785	None	1.0	D	0.533	0.463	0.590966807702	gnomAD-4.0.0	4.96173E-06	None	None	None	None	I	None	1.06855E-04	0	None	0	0	None	0	0	0	0	0
P/L	None	None	0.961	N	0.503	0.355	0.682110513636	gnomAD-4.0.0	6.84815E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99878E-07	0	0
P/R	None	None	0.997	N	0.531	0.451	0.535774538982	gnomAD-4.0.0	2.05445E-06	None	None	None	None	I	None	0	2.24638E-05	None	0	0	None	0	0	1.79976E-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	0.1719	likely_benign	0.1453	benign	-0.45	Destabilizing	0.953	D	0.415	neutral	N	0.494073347	None	None	I
P/C	0.7382	likely_pathogenic	0.7372	pathogenic	-0.656	Destabilizing	1.0	D	0.553	neutral	None	None	None	None	I
P/D	0.5276	ambiguous	0.5036	ambiguous	-0.34	Destabilizing	0.998	D	0.394	neutral	None	None	None	None	I
P/E	0.3947	ambiguous	0.3666	ambiguous	-0.461	Destabilizing	0.993	D	0.413	neutral	None	None	None	None	I
P/F	0.7066	likely_pathogenic	0.6847	pathogenic	-0.731	Destabilizing	0.998	D	0.55	neutral	None	None	None	None	I
P/G	0.4978	ambiguous	0.4642	ambiguous	-0.56	Destabilizing	0.993	D	0.507	neutral	None	None	None	None	I
P/H	0.3756	ambiguous	0.3431	ambiguous	-0.177	Destabilizing	1.0	D	0.533	neutral	D	0.52234582	None	None	I
P/I	0.513	ambiguous	0.4888	ambiguous	-0.31	Destabilizing	0.971	D	0.524	neutral	None	None	None	None	I
P/K	0.5063	ambiguous	0.4511	ambiguous	-0.462	Destabilizing	0.993	D	0.41	neutral	None	None	None	None	I
P/L	0.2778	likely_benign	0.2529	benign	-0.31	Destabilizing	0.961	D	0.503	neutral	N	0.495087306	None	None	I
P/M	0.5254	ambiguous	0.5017	ambiguous	-0.418	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	I
P/N	0.4561	ambiguous	0.4375	ambiguous	-0.191	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	I
P/Q	0.3056	likely_benign	0.2692	benign	-0.436	Destabilizing	0.999	D	0.413	neutral	None	None	None	None	I
P/R	0.358	ambiguous	0.3053	benign	0.042	Stabilizing	0.997	D	0.531	neutral	N	0.492124791	None	None	I
P/S	0.2329	likely_benign	0.2182	benign	-0.517	Destabilizing	0.961	D	0.419	neutral	N	0.504366469	None	None	I
P/T	0.1954	likely_benign	0.1909	benign	-0.54	Destabilizing	0.219	N	0.201	neutral	D	0.52766958	None	None	I
P/V	0.3528	ambiguous	0.3306	benign	-0.323	Destabilizing	0.469	N	0.357	neutral	None	None	None	None	I
P/W	0.8617	likely_pathogenic	0.8561	pathogenic	-0.805	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
P/Y	0.6591	likely_pathogenic	0.6312	pathogenic	-0.513	Destabilizing	0.999	D	0.55	neutral	None	None	None	None	I

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.