TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27714	83365;83366;83367	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
N2AB	26073	78442;78443;78444	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
N2A	25146	75661;75662;75663	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
N2B	18649	56170;56171;56172	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
Novex-1	18774	56545;56546;56547	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
Novex-2	18841	56746;56747;56748	chr2:178562992;178562991;178562990	chr2:179427719;179427718;179427717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-141
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3184
• 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
G/D	None	None	0.935	N	0.431	0.309	0.316494231283	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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
G/A	0.2175	likely_benign	0.2104	benign	-0.269	Destabilizing	0.025	N	0.349	neutral	N	0.489589896	None	None	N
G/C	0.3507	ambiguous	0.3298	benign	-0.946	Destabilizing	0.995	D	0.629	neutral	D	0.526358291	None	None	N
G/D	0.2971	likely_benign	0.2773	benign	-0.686	Destabilizing	0.935	D	0.431	neutral	N	0.51077733	None	None	N
G/E	0.3524	ambiguous	0.3369	benign	-0.839	Destabilizing	0.975	D	0.483	neutral	None	None	None	None	N
G/F	0.8014	likely_pathogenic	0.7774	pathogenic	-0.971	Destabilizing	0.987	D	0.634	neutral	None	None	None	None	N
G/H	0.6036	likely_pathogenic	0.569	pathogenic	-0.426	Destabilizing	0.997	D	0.566	neutral	None	None	None	None	N
G/I	0.4872	ambiguous	0.4686	ambiguous	-0.44	Destabilizing	0.975	D	0.631	neutral	None	None	None	None	N
G/K	0.6668	likely_pathogenic	0.6321	pathogenic	-0.878	Destabilizing	0.975	D	0.477	neutral	None	None	None	None	N
G/L	0.686	likely_pathogenic	0.6717	pathogenic	-0.44	Destabilizing	0.95	D	0.586	neutral	None	None	None	None	N
G/M	0.6231	likely_pathogenic	0.6006	pathogenic	-0.642	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
G/N	0.2811	likely_benign	0.2703	benign	-0.534	Destabilizing	0.033	N	0.347	neutral	None	None	None	None	N
G/P	0.9448	likely_pathogenic	0.9394	pathogenic	-0.353	Destabilizing	0.987	D	0.546	neutral	None	None	None	None	N
G/Q	0.5426	ambiguous	0.5095	ambiguous	-0.799	Destabilizing	0.975	D	0.549	neutral	None	None	None	None	N
G/R	0.599	likely_pathogenic	0.5571	ambiguous	-0.426	Destabilizing	0.967	D	0.544	neutral	N	0.513489562	None	None	N
G/S	0.1411	likely_benign	0.1371	benign	-0.655	Destabilizing	0.099	N	0.351	neutral	D	0.531360459	None	None	N
G/T	0.2277	likely_benign	0.2149	benign	-0.742	Destabilizing	0.845	D	0.475	neutral	None	None	None	None	N
G/V	0.3383	likely_benign	0.3235	benign	-0.353	Destabilizing	0.935	D	0.602	neutral	D	0.525765425	None	None	N
G/W	0.7415	likely_pathogenic	0.703	pathogenic	-1.118	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
G/Y	0.6349	likely_pathogenic	0.6064	pathogenic	-0.79	Destabilizing	0.999	D	0.63	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.