TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5387	16384;16385;16386	chr2:178733017;178733016;178733015	chr2:179597744;179597743;179597742
N2AB	5070	15433;15434;15435	chr2:178733017;178733016;178733015	chr2:179597744;179597743;179597742
N2A	4143	12652;12653;12654	chr2:178733017;178733016;178733015	chr2:179597744;179597743;179597742
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-37
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7766
• 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
R/G	rs371501460	-0.16	0.425	N	0.447	0.33	0.492542987314	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	2.87687E-04	0	0
R/G	rs371501460	-0.16	0.425	N	0.447	0.33	0.492542987314	gnomAD-4.0.0	1.36867E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.74728E-05	0	0	0	0
R/T	rs748155563	0.286	0.003	N	0.189	0.292	0.340273420219	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	2.03488E-04	None	0	5.61E-05	None	0	None	0	0	0
R/T	rs748155563	0.286	0.003	N	0.189	0.292	0.340273420219	gnomAD-4.0.0	6.04941E-05	None	None	None	None	I	None	0	2.05997E-04	None	0	7.78556E-04	None	0	0	0	0	3.02608E-05

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
R/A	0.1556	likely_benign	0.1548	benign	-0.006	Destabilizing	0.176	N	0.303	neutral	None	None	None	None	I
R/C	0.1772	likely_benign	0.1676	benign	-0.175	Destabilizing	0.995	D	0.444	neutral	None	None	None	None	I
R/D	0.3027	likely_benign	0.3005	benign	-0.134	Destabilizing	0.704	D	0.531	neutral	None	None	None	None	I
R/E	0.1661	likely_benign	0.1637	benign	-0.082	Destabilizing	0.329	N	0.369	neutral	None	None	None	None	I
R/F	0.3628	ambiguous	0.3623	ambiguous	-0.26	Destabilizing	0.944	D	0.483	neutral	None	None	None	None	I
R/G	0.1328	likely_benign	0.1296	benign	-0.181	Destabilizing	0.425	N	0.447	neutral	N	0.430105748	None	None	I
R/H	0.0783	likely_benign	0.0755	benign	-0.625	Destabilizing	0.981	D	0.493	neutral	None	None	None	None	I
R/I	0.1584	likely_benign	0.1512	benign	0.417	Stabilizing	0.704	D	0.576	neutral	None	None	None	None	I
R/K	0.0771	likely_benign	0.0735	benign	-0.097	Destabilizing	0.001	N	0.126	neutral	N	0.426582653	None	None	I
R/L	0.1367	likely_benign	0.1355	benign	0.417	Stabilizing	0.329	N	0.423	neutral	None	None	None	None	I
R/M	0.1478	likely_benign	0.1411	benign	0.027	Stabilizing	0.975	D	0.501	neutral	N	0.495098589	None	None	I
R/N	0.2321	likely_benign	0.225	benign	0.118	Stabilizing	0.495	N	0.41	neutral	None	None	None	None	I
R/P	0.7243	likely_pathogenic	0.7092	pathogenic	0.296	Stabilizing	0.828	D	0.581	neutral	None	None	None	None	I
R/Q	0.0766	likely_benign	0.0745	benign	0.01	Stabilizing	0.704	D	0.439	neutral	None	None	None	None	I
R/S	0.171	likely_benign	0.1666	benign	-0.203	Destabilizing	0.27	N	0.353	neutral	N	0.407322102	None	None	I
R/T	0.0829	likely_benign	0.0778	benign	-0.028	Destabilizing	0.003	N	0.189	neutral	N	0.400532202	None	None	I
R/V	0.176	likely_benign	0.1719	benign	0.296	Stabilizing	0.329	N	0.453	neutral	None	None	None	None	I
R/W	0.1675	likely_benign	0.1624	benign	-0.335	Destabilizing	0.993	D	0.445	neutral	D	0.532712827	None	None	I
R/Y	0.2603	likely_benign	0.2591	benign	0.073	Stabilizing	0.981	D	0.517	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.