TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15618	47077;47078;47079	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
N2AB	13977	42154;42155;42156	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
N2A	13050	39373;39374;39375	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
N2B	6553	19882;19883;19884	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
Novex-1	6678	20257;20258;20259	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
Novex-2	6745	20458;20459;20460	chr2:178618698;178618697;178618696	chr2:179483425;179483424;179483423
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-108
• Domain position: 51
• Structural Position: 134
• Q(SASA): 0.564
• 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/K	None	None	0.324	N	0.422	0.242	0.326881540566	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.1322	likely_benign	0.1598	benign	-0.764	Destabilizing	0.324	N	0.416	neutral	N	0.493701351	None	None	N
E/C	0.7089	likely_pathogenic	0.7875	pathogenic	-0.347	Destabilizing	0.981	D	0.497	neutral	None	None	None	None	N
E/D	0.0805	likely_benign	0.0999	benign	-0.609	Destabilizing	None	N	0.13	neutral	N	0.396135264	None	None	N
E/F	0.5518	ambiguous	0.6305	pathogenic	-0.448	Destabilizing	0.932	D	0.457	neutral	None	None	None	None	N
E/G	0.104	likely_benign	0.1202	benign	-1.023	Destabilizing	0.193	N	0.438	neutral	N	0.453366357	None	None	N
E/H	0.3419	ambiguous	0.3959	ambiguous	-0.381	Destabilizing	0.818	D	0.391	neutral	None	None	None	None	N
E/I	0.2985	likely_benign	0.3777	ambiguous	-0.09	Destabilizing	0.818	D	0.455	neutral	None	None	None	None	N
E/K	0.139	likely_benign	0.1693	benign	-0.267	Destabilizing	0.324	N	0.422	neutral	N	0.491130694	None	None	N
E/L	0.2928	likely_benign	0.3691	ambiguous	-0.09	Destabilizing	0.818	D	0.431	neutral	None	None	None	None	N
E/M	0.374	ambiguous	0.4565	ambiguous	0.14	Stabilizing	0.981	D	0.449	neutral	None	None	None	None	N
E/N	0.1293	likely_benign	0.1489	benign	-0.589	Destabilizing	0.002	N	0.217	neutral	None	None	None	None	N
E/P	0.6268	likely_pathogenic	0.721	pathogenic	-0.295	Destabilizing	0.818	D	0.423	neutral	None	None	None	None	N
E/Q	0.1274	likely_benign	0.1436	benign	-0.531	Destabilizing	0.324	N	0.395	neutral	N	0.493701351	None	None	N
E/R	0.2347	likely_benign	0.2747	benign	0.059	Stabilizing	0.69	D	0.382	neutral	None	None	None	None	N
E/S	0.1231	likely_benign	0.1435	benign	-0.817	Destabilizing	0.241	N	0.397	neutral	None	None	None	None	N
E/T	0.1437	likely_benign	0.1661	benign	-0.614	Destabilizing	0.388	N	0.422	neutral	None	None	None	None	N
E/V	0.204	likely_benign	0.2616	benign	-0.295	Destabilizing	0.773	D	0.432	neutral	N	0.494158355	None	None	N
E/W	0.776	likely_pathogenic	0.8503	pathogenic	-0.22	Destabilizing	0.981	D	0.581	neutral	None	None	None	None	N
E/Y	0.4283	ambiguous	0.4892	ambiguous	-0.214	Destabilizing	0.932	D	0.45	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.