TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29724	89395;89396;89397	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
N2AB	28083	84472;84473;84474	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
N2A	27156	81691;81692;81693	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
N2B	20659	62200;62201;62202	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
Novex-1	20784	62575;62576;62577	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
Novex-2	20851	62776;62777;62778	chr2:178553941;178553940;178553939	chr2:179418668;179418667;179418666
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: Fn3-104
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.6086
• 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/D	None	None	None	N	0.198	0.051	0.124217242631	gnomAD-4.0.0	1.61543E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88017E-06	0	0
E/K	rs370918981	-0.087	0.058	N	0.529	0.131	None	gnomAD-2.1.1	1.47E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.38E-05	1.43885E-04
E/K	rs370918981	-0.087	0.058	N	0.529	0.131	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78011E-04
E/K	rs370918981	-0.087	0.058	N	0.529	0.131	None	gnomAD-4.0.0	1.68287E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.12378E-05	0	3.2175E-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	0.0931	likely_benign	0.0978	benign	-0.637	Destabilizing	0.025	N	0.518	neutral	N	0.465836396	None	None	N
E/C	0.5992	likely_pathogenic	0.5703	pathogenic	-0.538	Destabilizing	0.869	D	0.497	neutral	None	None	None	None	N
E/D	0.0621	likely_benign	0.0606	benign	-0.55	Destabilizing	None	N	0.198	neutral	N	0.431955895	None	None	N
E/F	0.5584	ambiguous	0.5414	ambiguous	-0.039	Destabilizing	0.366	N	0.593	neutral	None	None	None	None	N
E/G	0.1188	likely_benign	0.1211	benign	-0.893	Destabilizing	0.025	N	0.523	neutral	N	0.479632412	None	None	N
E/H	0.3142	likely_benign	0.297	benign	0.401	Stabilizing	0.366	N	0.627	neutral	None	None	None	None	N
E/I	0.189	likely_benign	0.1965	benign	0.038	Stabilizing	0.001	N	0.363	neutral	None	None	None	None	N
E/K	0.1326	likely_benign	0.143	benign	0.01	Stabilizing	0.058	N	0.529	neutral	N	0.48511559	None	None	N
E/L	0.2263	likely_benign	0.2303	benign	0.038	Stabilizing	0.039	N	0.506	neutral	None	None	None	None	N
E/M	0.3213	likely_benign	0.3285	benign	0.018	Stabilizing	0.366	N	0.543	neutral	None	None	None	None	N
E/N	0.1163	likely_benign	0.1218	benign	-0.668	Destabilizing	0.039	N	0.557	neutral	None	None	None	None	N
E/P	0.2128	likely_benign	0.2346	benign	-0.168	Destabilizing	0.141	N	0.647	neutral	None	None	None	None	N
E/Q	0.1288	likely_benign	0.1306	benign	-0.56	Destabilizing	0.058	N	0.576	neutral	N	0.488809256	None	None	N
E/R	0.2185	likely_benign	0.2199	benign	0.486	Stabilizing	0.221	N	0.581	neutral	None	None	None	None	N
E/S	0.1109	likely_benign	0.1135	benign	-0.834	Destabilizing	0.016	N	0.602	neutral	None	None	None	None	N
E/T	0.1399	likely_benign	0.1511	benign	-0.599	Destabilizing	0.075	N	0.591	neutral	None	None	None	None	N
E/V	0.1191	likely_benign	0.1232	benign	-0.168	Destabilizing	0.012	N	0.473	neutral	N	0.451848378	None	None	N
E/W	0.803	likely_pathogenic	0.7838	pathogenic	0.28	Stabilizing	0.869	D	0.541	neutral	None	None	None	None	N
E/Y	0.3652	ambiguous	0.3554	ambiguous	0.242	Stabilizing	0.637	D	0.59	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.