TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35371	106336;106337;106338	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
N2AB	33730	101413;101414;101415	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
N2A	32803	98632;98633;98634	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
N2B	26306	79141;79142;79143	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
Novex-1	26431	79516;79517;79518	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
Novex-2	26498	79717;79718;79719	chr2:178530504;178530503;178530502	chr2:179395231;179395230;179395229
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-165
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.458
• 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
N/S	rs1200663369	-0.482	None	N	0.207	0.065	0.0716867268079	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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
N/A	0.1656	likely_benign	0.1824	benign	-0.683	Destabilizing	0.007	N	0.482	neutral	None	None	None	None	N
N/C	0.2125	likely_benign	0.2457	benign	0.134	Stabilizing	0.676	D	0.637	neutral	None	None	None	None	N
N/D	0.1295	likely_benign	0.1335	benign	-0.21	Destabilizing	0.012	N	0.482	neutral	N	0.499560259	None	None	N
N/E	0.3393	likely_benign	0.3647	ambiguous	-0.141	Destabilizing	0.016	N	0.493	neutral	None	None	None	None	N
N/F	0.4354	ambiguous	0.4633	ambiguous	-0.457	Destabilizing	0.356	N	0.66	neutral	None	None	None	None	N
N/G	0.2396	likely_benign	0.2612	benign	-1.003	Destabilizing	0.016	N	0.376	neutral	None	None	None	None	N
N/H	0.0945	likely_benign	0.0933	benign	-0.813	Destabilizing	0.295	N	0.591	neutral	N	0.485212257	None	None	N
N/I	0.16	likely_benign	0.1726	benign	0.118	Stabilizing	0.055	N	0.679	prob.neutral	D	0.522591834	None	None	N
N/K	0.2442	likely_benign	0.2529	benign	-0.269	Destabilizing	0.012	N	0.48	neutral	N	0.494959729	None	None	N
N/L	0.2039	likely_benign	0.219	benign	0.118	Stabilizing	0.038	N	0.593	neutral	None	None	None	None	N
N/M	0.304	likely_benign	0.323	benign	0.463	Stabilizing	0.628	D	0.633	neutral	None	None	None	None	N
N/P	0.5077	ambiguous	0.5758	pathogenic	-0.118	Destabilizing	0.072	N	0.673	neutral	None	None	None	None	N
N/Q	0.285	likely_benign	0.3055	benign	-0.708	Destabilizing	0.072	N	0.569	neutral	None	None	None	None	N
N/R	0.2665	likely_benign	0.2757	benign	-0.327	Destabilizing	0.072	N	0.549	neutral	None	None	None	None	N
N/S	0.0601	likely_benign	0.0639	benign	-0.717	Destabilizing	None	N	0.207	neutral	N	0.445379058	None	None	N
N/T	0.0882	likely_benign	0.093	benign	-0.467	Destabilizing	None	N	0.182	neutral	N	0.466370405	None	None	N
N/V	0.1715	likely_benign	0.1823	benign	-0.118	Destabilizing	0.038	N	0.624	neutral	None	None	None	None	N
N/W	0.73	likely_pathogenic	0.77	pathogenic	-0.261	Destabilizing	0.864	D	0.65	neutral	None	None	None	None	N
N/Y	0.1566	likely_benign	0.1608	benign	-0.07	Destabilizing	0.295	N	0.654	neutral	N	0.507854455	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.