TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25183	75772;75773;75774	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
N2AB	23542	70849;70850;70851	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
N2A	22615	68068;68069;68070	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
N2B	16118	48577;48578;48579	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
Novex-1	16243	48952;48953;48954	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
Novex-2	16310	49153;49154;49155	chr2:178570585;178570584;178570583	chr2:179435312;179435311;179435310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-134
• Domain position: 73
• Structural Position: 155
• Q(SASA): 0.2238
• 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
I/K	None	None	0.175	N	0.577	0.176	0.449764926163	gnomAD-4.0.0	1.02655E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.8735E-05	0	1.16945E-05	0	1.65728E-05
I/V	rs1180372550	None	None	N	0.17	0.053	0.180583059064	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	3.16456E-03	0	0	0
I/V	rs1180372550	None	None	N	0.17	0.053	0.180583059064	gnomAD-4.0.0	2.56343E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	4.48833E-04	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
I/A	0.1917	likely_benign	0.247	benign	-2.131	Highly Destabilizing	0.055	N	0.499	neutral	None	None	None	None	N
I/C	0.3874	ambiguous	0.4778	ambiguous	-1.452	Destabilizing	0.883	D	0.549	neutral	None	None	None	None	N
I/D	0.4472	ambiguous	0.5399	ambiguous	-1.785	Destabilizing	0.124	N	0.577	neutral	None	None	None	None	N
I/E	0.3227	likely_benign	0.3906	ambiguous	-1.606	Destabilizing	0.22	N	0.582	neutral	None	None	None	None	N
I/F	0.1217	likely_benign	0.1466	benign	-1.198	Destabilizing	0.497	N	0.539	neutral	None	None	None	None	N
I/G	0.4475	ambiguous	0.5498	ambiguous	-2.635	Highly Destabilizing	0.124	N	0.542	neutral	None	None	None	None	N
I/H	0.2295	likely_benign	0.2699	benign	-1.966	Destabilizing	0.667	D	0.617	neutral	None	None	None	None	N
I/K	0.1934	likely_benign	0.2355	benign	-1.474	Destabilizing	0.175	N	0.577	neutral	N	0.450493223	None	None	N
I/L	0.094	likely_benign	0.109	benign	-0.716	Destabilizing	0.019	N	0.355	neutral	N	0.486491308	None	None	N
I/M	0.0846	likely_benign	0.0986	benign	-0.701	Destabilizing	0.427	N	0.524	neutral	N	0.476410388	None	None	N
I/N	0.1363	likely_benign	0.1645	benign	-1.647	Destabilizing	0.001	N	0.551	neutral	None	None	None	None	N
I/P	0.9157	likely_pathogenic	0.9424	pathogenic	-1.163	Destabilizing	0.859	D	0.625	neutral	None	None	None	None	N
I/Q	0.2134	likely_benign	0.2603	benign	-1.563	Destabilizing	0.667	D	0.617	neutral	None	None	None	None	N
I/R	0.1469	likely_benign	0.1842	benign	-1.185	Destabilizing	0.427	N	0.627	neutral	N	0.457245837	None	None	N
I/S	0.1297	likely_benign	0.1635	benign	-2.421	Highly Destabilizing	0.055	N	0.497	neutral	None	None	None	None	N
I/T	0.0848	likely_benign	0.1008	benign	-2.098	Highly Destabilizing	0.001	N	0.323	neutral	N	0.349075435	None	None	N
I/V	0.0604	likely_benign	0.0679	benign	-1.163	Destabilizing	None	N	0.17	neutral	N	0.43002195	None	None	N
I/W	0.6551	likely_pathogenic	0.7097	pathogenic	-1.475	Destabilizing	0.958	D	0.664	neutral	None	None	None	None	N
I/Y	0.3047	likely_benign	0.3641	ambiguous	-1.178	Destabilizing	0.667	D	0.565	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.