TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27823	83692;83693;83694	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
N2AB	26182	78769;78770;78771	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
N2A	25255	75988;75989;75990	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
N2B	18758	56497;56498;56499	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
Novex-1	18883	56872;56873;56874	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
Novex-2	18950	57073;57074;57075	chr2:178562665;178562664;178562663	chr2:179427392;179427391;179427390
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-90
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.2961
• 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
T/A	rs940216066	-0.809	0.001	N	0.297	0.325	0.283761946502	gnomAD-2.1.1	4.28E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.25E-06	0
T/A	rs940216066	-0.809	0.001	N	0.297	0.325	0.283761946502	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs940216066	-0.809	0.001	N	0.297	0.325	0.283761946502	gnomAD-4.0.0	3.9291E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.28905E-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
T/A	0.0823	likely_benign	0.0795	benign	-0.886	Destabilizing	0.001	N	0.297	neutral	N	0.500615535	None	None	N
T/C	0.1568	likely_benign	0.169	benign	-0.384	Destabilizing	0.92	D	0.497	neutral	None	None	None	None	N
T/D	0.3604	ambiguous	0.3922	ambiguous	-0.231	Destabilizing	0.008	N	0.408	neutral	None	None	None	None	N
T/E	0.4522	ambiguous	0.4617	ambiguous	-0.105	Destabilizing	0.027	N	0.411	neutral	None	None	None	None	N
T/F	0.3081	likely_benign	0.2946	benign	-0.821	Destabilizing	0.916	D	0.543	neutral	None	None	None	None	N
T/G	0.1412	likely_benign	0.1475	benign	-1.239	Destabilizing	0.065	N	0.429	neutral	None	None	None	None	N
T/H	0.1773	likely_benign	0.1899	benign	-1.311	Destabilizing	0.398	N	0.541	neutral	None	None	None	None	N
T/I	0.2129	likely_benign	0.2084	benign	0.005	Stabilizing	0.224	N	0.557	neutral	N	0.504476649	None	None	N
T/K	0.3396	likely_benign	0.3338	benign	-0.234	Destabilizing	0.037	N	0.399	neutral	None	None	None	None	N
T/L	0.08	likely_benign	0.0777	benign	0.005	Stabilizing	0.072	N	0.418	neutral	None	None	None	None	N
T/M	0.0888	likely_benign	0.0828	benign	0.013	Stabilizing	0.803	D	0.505	neutral	None	None	None	None	N
T/N	0.0407	likely_benign	0.043	benign	-0.63	Destabilizing	None	N	0.203	neutral	N	0.490025551	None	None	N
T/P	0.0976	likely_benign	0.0947	benign	-0.259	Destabilizing	0.058	N	0.508	neutral	N	0.479864708	None	None	N
T/Q	0.2335	likely_benign	0.2336	benign	-0.51	Destabilizing	0.081	N	0.485	neutral	None	None	None	None	N
T/R	0.3192	likely_benign	0.3046	benign	-0.292	Destabilizing	0.002	N	0.288	neutral	None	None	None	None	N
T/S	0.0794	likely_benign	0.0822	benign	-0.965	Destabilizing	None	N	0.213	neutral	N	0.496563384	None	None	N
T/V	0.1609	likely_benign	0.1522	benign	-0.259	Destabilizing	0.119	N	0.324	neutral	None	None	None	None	N
T/W	0.6588	likely_pathogenic	0.6376	pathogenic	-0.88	Destabilizing	0.976	D	0.569	neutral	None	None	None	None	N
T/Y	0.1884	likely_benign	0.1944	benign	-0.524	Destabilizing	0.916	D	0.547	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.