TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25639	77140;77141;77142	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
N2AB	23998	72217;72218;72219	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
N2A	23071	69436;69437;69438	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
N2B	16574	49945;49946;49947	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
Novex-1	16699	50320;50321;50322	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
Novex-2	16766	50521;50522;50523	chr2:178569217;178569216;178569215	chr2:179433944;179433943;179433942
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-74
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1756
• 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
E/Q	None	None	1.0	D	0.749	0.371	0.242244723065	gnomAD-4.0.0	1.61054E-06	None	None	None	None	N	None	0	2.32786E-05	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
E/A	0.9073	likely_pathogenic	0.8923	pathogenic	-1.607	Destabilizing	1.0	D	0.698	prob.neutral	D	0.531241411	None	None	N
E/C	0.9901	likely_pathogenic	0.9895	pathogenic	-0.868	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/D	0.7606	likely_pathogenic	0.7833	pathogenic	-1.549	Destabilizing	0.998	D	0.659	neutral	N	0.477182136	None	None	N
E/F	0.9923	likely_pathogenic	0.9933	pathogenic	-1.213	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/G	0.9097	likely_pathogenic	0.9108	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.778	deleterious	D	0.544372143	None	None	N
E/H	0.9752	likely_pathogenic	0.9758	pathogenic	-1.199	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/I	0.9827	likely_pathogenic	0.9806	pathogenic	-0.444	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
E/K	0.9523	likely_pathogenic	0.9484	pathogenic	-1.463	Destabilizing	1.0	D	0.697	prob.neutral	N	0.518617658	None	None	N
E/L	0.9719	likely_pathogenic	0.9707	pathogenic	-0.444	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.9665	likely_pathogenic	0.9646	pathogenic	0.288	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/N	0.9662	likely_pathogenic	0.9671	pathogenic	-1.692	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.816	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Q	0.5236	ambiguous	0.475	ambiguous	-1.455	Destabilizing	1.0	D	0.749	deleterious	D	0.522732615	None	None	N
E/R	0.9626	likely_pathogenic	0.9598	pathogenic	-1.237	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/S	0.8935	likely_pathogenic	0.8876	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/T	0.9647	likely_pathogenic	0.9601	pathogenic	-1.995	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/V	0.9523	likely_pathogenic	0.9464	pathogenic	-0.816	Destabilizing	1.0	D	0.786	deleterious	D	0.528381029	None	None	N
E/W	0.9962	likely_pathogenic	0.9966	pathogenic	-1.157	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
E/Y	0.9876	likely_pathogenic	0.989	pathogenic	-0.979	Destabilizing	1.0	D	0.813	deleterious	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.