TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30786	92581;92582;92583	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
N2AB	29145	87658;87659;87660	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
N2A	28218	84877;84878;84879	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
N2B	21721	65386;65387;65388	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
Novex-1	21846	65761;65762;65763	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
Novex-2	21913	65962;65963;65964	chr2:178549270;178549269;178549268	chr2:179413997;179413996;179413995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-112
• Domain position: 68
• Structural Position: 98
• Q(SASA): 0.3972
• 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/R	None	None	0.667	N	0.576	0.122	0.21737058555	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0796	likely_benign	0.0811	benign	-0.909	Destabilizing	0.055	N	0.417	neutral	N	0.501626624	None	None	N
T/C	0.3271	likely_benign	0.3724	ambiguous	-0.471	Destabilizing	0.909	D	0.569	neutral	None	None	None	None	N
T/D	0.5071	ambiguous	0.5391	ambiguous	-0.016	Destabilizing	0.726	D	0.561	neutral	None	None	None	None	N
T/E	0.3346	likely_benign	0.3724	ambiguous	-0.039	Destabilizing	0.726	D	0.533	neutral	None	None	None	None	N
T/F	0.1919	likely_benign	0.2185	benign	-1.127	Destabilizing	0.567	D	0.603	neutral	None	None	None	None	N
T/G	0.2394	likely_benign	0.2567	benign	-1.131	Destabilizing	0.726	D	0.505	neutral	None	None	None	None	N
T/H	0.2586	likely_benign	0.2678	benign	-1.357	Destabilizing	0.968	D	0.587	neutral	None	None	None	None	N
T/I	0.0885	likely_benign	0.0934	benign	-0.419	Destabilizing	0.001	N	0.183	neutral	N	0.446293416	None	None	N
T/K	0.2363	likely_benign	0.2543	benign	-0.619	Destabilizing	0.667	D	0.535	neutral	N	0.457160984	None	None	N
T/L	0.0598	likely_benign	0.0608	benign	-0.419	Destabilizing	0.026	N	0.447	neutral	None	None	None	None	N
T/M	0.0693	likely_benign	0.0712	benign	-0.059	Destabilizing	0.567	D	0.567	neutral	None	None	None	None	N
T/N	0.1331	likely_benign	0.1275	benign	-0.489	Destabilizing	0.89	D	0.523	neutral	None	None	None	None	N
T/P	0.2384	likely_benign	0.2199	benign	-0.551	Destabilizing	0.859	D	0.576	neutral	N	0.474953637	None	None	N
T/Q	0.2065	likely_benign	0.2168	benign	-0.701	Destabilizing	0.89	D	0.567	neutral	None	None	None	None	N
T/R	0.1976	likely_benign	0.2191	benign	-0.324	Destabilizing	0.667	D	0.576	neutral	N	0.472149079	None	None	N
T/S	0.1135	likely_benign	0.1154	benign	-0.813	Destabilizing	0.22	N	0.411	neutral	N	0.461761514	None	None	N
T/V	0.0801	likely_benign	0.0863	benign	-0.551	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
T/W	0.4881	ambiguous	0.524	ambiguous	-1.017	Destabilizing	0.968	D	0.65	neutral	None	None	None	None	N
T/Y	0.2642	likely_benign	0.2872	benign	-0.795	Destabilizing	0.726	D	0.588	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.