TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8163	24712;24713;24714	chr2:178718713;178718712;178718711	chr2:179583440;179583439;179583438
N2AB	7846	23761;23762;23763	chr2:178718713;178718712;178718711	chr2:179583440;179583439;179583438
N2A	6919	20980;20981;20982	chr2:178718713;178718712;178718711	chr2:179583440;179583439;179583438
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-66
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.0951
• 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/I	rs1019848168	0.394	0.062	D	0.667	0.234	0.368743488249	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
T/I	rs1019848168	0.394	0.062	D	0.667	0.234	0.368743488249	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1019848168	0.394	0.062	D	0.667	0.234	0.368743488249	gnomAD-4.0.0	1.31446E-05	None	None	None	None	N	None	4.82509E-05	0	None	0	0	None	0	0	0	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	0.0615	likely_benign	0.0699	benign	-1.032	Destabilizing	None	N	0.153	neutral	N	0.420056539	None	None	N
T/C	0.4126	ambiguous	0.4557	ambiguous	-0.853	Destabilizing	0.824	D	0.693	prob.neutral	None	None	None	None	N
T/D	0.8011	likely_pathogenic	0.8552	pathogenic	-1.797	Destabilizing	0.38	N	0.737	prob.delet.	None	None	None	None	N
T/E	0.7198	likely_pathogenic	0.7702	pathogenic	-1.628	Destabilizing	0.149	N	0.714	prob.delet.	None	None	None	None	N
T/F	0.5148	ambiguous	0.5469	ambiguous	-0.823	Destabilizing	0.555	D	0.746	deleterious	None	None	None	None	N
T/G	0.2932	likely_benign	0.3354	benign	-1.435	Destabilizing	0.081	N	0.654	neutral	None	None	None	None	N
T/H	0.604	likely_pathogenic	0.6649	pathogenic	-1.724	Destabilizing	0.935	D	0.685	prob.neutral	None	None	None	None	N
T/I	0.249	likely_benign	0.3336	benign	0.011	Stabilizing	0.062	N	0.667	neutral	D	0.531824606	None	None	N
T/K	0.5953	likely_pathogenic	0.6273	pathogenic	-0.757	Destabilizing	0.117	N	0.717	prob.delet.	N	0.51757288	None	None	N
T/L	0.1919	likely_benign	0.1987	benign	0.011	Stabilizing	0.035	N	0.603	neutral	None	None	None	None	N
T/M	0.1439	likely_benign	0.1288	benign	0.214	Stabilizing	0.555	D	0.708	prob.delet.	None	None	None	None	N
T/N	0.3696	ambiguous	0.4463	ambiguous	-1.485	Destabilizing	0.555	D	0.683	prob.neutral	None	None	None	None	N
T/P	0.6754	likely_pathogenic	0.7227	pathogenic	-0.304	Destabilizing	0.317	N	0.747	deleterious	N	0.51782637	None	None	N
T/Q	0.5406	ambiguous	0.5715	pathogenic	-1.311	Destabilizing	0.555	D	0.742	deleterious	None	None	None	None	N
T/R	0.4574	ambiguous	0.507	ambiguous	-0.909	Destabilizing	0.317	N	0.741	deleterious	N	0.51757288	None	None	N
T/S	0.1354	likely_benign	0.151	benign	-1.606	Destabilizing	0.027	N	0.553	neutral	N	0.513356276	None	None	N
T/V	0.1499	likely_benign	0.1738	benign	-0.304	Destabilizing	0.002	N	0.209	neutral	None	None	None	None	N
T/W	0.8749	likely_pathogenic	0.8894	pathogenic	-1.022	Destabilizing	0.935	D	0.704	prob.neutral	None	None	None	None	N
T/Y	0.6527	likely_pathogenic	0.7079	pathogenic	-0.639	Destabilizing	0.555	D	0.738	prob.delet.	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.