TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7992	24199;24200;24201	chr2:178719416;178719415;178719414	chr2:179584143;179584142;179584141
N2AB	7675	23248;23249;23250	chr2:178719416;178719415;178719414	chr2:179584143;179584142;179584141
N2A	6748	20467;20468;20469	chr2:178719416;178719415;178719414	chr2:179584143;179584142;179584141
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-65
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6787
• 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
K/I	None	None	0.852	N	0.426	0.443	0.728599915167	gnomAD-4.0.0	1.5926E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-05	0
K/Q	rs1420514205	0.223	0.92	N	0.391	0.316	0.32082282376	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/Q	rs1420514205	0.223	0.92	N	0.391	0.316	0.32082282376	gnomAD-4.0.0	1.59264E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4332E-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
K/A	0.3884	ambiguous	0.4081	ambiguous	0.058	Stabilizing	0.863	D	0.361	neutral	None	None	None	None	I
K/C	0.7477	likely_pathogenic	0.7728	pathogenic	-0.346	Destabilizing	0.999	D	0.371	neutral	None	None	None	None	I
K/D	0.5763	likely_pathogenic	0.6	pathogenic	-0.249	Destabilizing	0.969	D	0.407	neutral	None	None	None	None	I
K/E	0.1714	likely_benign	0.1685	benign	-0.256	Destabilizing	0.92	D	0.377	neutral	N	0.496312097	None	None	I
K/F	0.8176	likely_pathogenic	0.8533	pathogenic	-0.225	Destabilizing	0.982	D	0.42	neutral	None	None	None	None	I
K/G	0.4268	ambiguous	0.4471	ambiguous	-0.095	Destabilizing	0.969	D	0.392	neutral	None	None	None	None	I
K/H	0.2986	likely_benign	0.335	benign	-0.234	Destabilizing	0.997	D	0.394	neutral	None	None	None	None	I
K/I	0.5059	ambiguous	0.5351	ambiguous	0.379	Stabilizing	0.852	D	0.426	neutral	N	0.500486264	None	None	I
K/L	0.4556	ambiguous	0.4882	ambiguous	0.379	Stabilizing	0.759	D	0.336	neutral	None	None	None	None	I
K/M	0.3334	likely_benign	0.3563	ambiguous	0.006	Stabilizing	0.579	D	0.245	neutral	None	None	None	None	I
K/N	0.4456	ambiguous	0.4646	ambiguous	0.093	Stabilizing	0.959	D	0.363	neutral	N	0.492977846	None	None	I
K/P	0.6586	likely_pathogenic	0.7203	pathogenic	0.297	Stabilizing	0.997	D	0.415	neutral	None	None	None	None	I
K/Q	0.133	likely_benign	0.1381	benign	-0.058	Destabilizing	0.92	D	0.391	neutral	N	0.476110183	None	None	I
K/R	0.0783	likely_benign	0.0796	benign	-0.069	Destabilizing	0.035	N	0.168	neutral	N	0.464989112	None	None	I
K/S	0.4225	ambiguous	0.4499	ambiguous	-0.277	Destabilizing	0.884	D	0.354	neutral	None	None	None	None	I
K/T	0.2279	likely_benign	0.2272	benign	-0.159	Destabilizing	0.134	N	0.137	neutral	N	0.497178889	None	None	I
K/V	0.4559	ambiguous	0.4752	ambiguous	0.297	Stabilizing	0.17	N	0.201	neutral	None	None	None	None	I
K/W	0.7075	likely_pathogenic	0.7683	pathogenic	-0.314	Destabilizing	0.999	D	0.396	neutral	None	None	None	None	I
K/Y	0.6704	likely_pathogenic	0.7141	pathogenic	0.039	Stabilizing	0.997	D	0.408	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.