TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30875	92848;92849;92850	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
N2AB	29234	87925;87926;87927	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
N2A	28307	85144;85145;85146	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
N2B	21810	65653;65654;65655	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
Novex-1	21935	66028;66029;66030	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
Novex-2	22002	66229;66230;66231	chr2:178549003;178549002;178549001	chr2:179413730;179413729;179413728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-113
• Domain position: 55
• Structural Position: 75
• 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
A/G	rs1248087390	-0.845	None	N	0.125	0.148	0.156986980423	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
A/G	rs1248087390	-0.845	None	N	0.125	0.148	0.156986980423	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/G	rs1248087390	-0.845	None	N	0.125	0.148	0.156986980423	gnomAD-4.0.0	3.22228E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.32258E-05	0	1.60113E-05
A/P	rs753079465	-0.411	None	N	0.272	0.051	0.0954503805726	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
A/P	rs753079465	-0.411	None	N	0.272	0.051	0.0954503805726	gnomAD-4.0.0	2.05253E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69829E-06	0	0
A/S	None	None	0.012	N	0.385	0.027	0.0762999501168	gnomAD-4.0.0	6.84175E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99431E-07	0	0
A/T	rs753079465	None	None	N	0.079	0.045	0.0846915920261	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs753079465	None	None	N	0.079	0.045	0.0846915920261	gnomAD-4.0.0	1.859E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.5427E-06	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
A/C	0.446	ambiguous	0.4934	ambiguous	-0.8	Destabilizing	0.864	D	0.455	neutral	None	None	None	None	N
A/D	0.3585	ambiguous	0.3677	ambiguous	-0.856	Destabilizing	0.072	N	0.558	neutral	None	None	None	None	N
A/E	0.3146	likely_benign	0.3177	benign	-0.968	Destabilizing	0.055	N	0.477	neutral	N	0.439788732	None	None	N
A/F	0.3472	ambiguous	0.3898	ambiguous	-1.027	Destabilizing	0.214	N	0.549	neutral	None	None	None	None	N
A/G	0.1533	likely_benign	0.1553	benign	-0.807	Destabilizing	None	N	0.125	neutral	N	0.36908064	None	None	N
A/H	0.4878	ambiguous	0.5344	ambiguous	-0.928	Destabilizing	0.864	D	0.521	neutral	None	None	None	None	N
A/I	0.181	likely_benign	0.201	benign	-0.435	Destabilizing	0.001	N	0.217	neutral	None	None	None	None	N
A/K	0.502	ambiguous	0.5349	ambiguous	-1.06	Destabilizing	0.072	N	0.481	neutral	None	None	None	None	N
A/L	0.1453	likely_benign	0.1648	benign	-0.435	Destabilizing	None	N	0.222	neutral	None	None	None	None	N
A/M	0.1953	likely_benign	0.2212	benign	-0.336	Destabilizing	0.214	N	0.474	neutral	None	None	None	None	N
A/N	0.2234	likely_benign	0.2439	benign	-0.669	Destabilizing	0.214	N	0.548	neutral	None	None	None	None	N
A/P	0.0938	likely_benign	0.094	benign	-0.47	Destabilizing	None	N	0.272	neutral	N	0.380799143	None	None	N
A/Q	0.3718	ambiguous	0.3923	ambiguous	-0.928	Destabilizing	0.356	N	0.474	neutral	None	None	None	None	N
A/R	0.4687	ambiguous	0.5073	ambiguous	-0.589	Destabilizing	0.214	N	0.493	neutral	None	None	None	None	N
A/S	0.1062	likely_benign	0.1078	benign	-0.927	Destabilizing	0.012	N	0.385	neutral	N	0.436287067	None	None	N
A/T	0.0791	likely_benign	0.0836	benign	-0.957	Destabilizing	None	N	0.079	neutral	N	0.390170775	None	None	N
A/V	0.1074	likely_benign	0.1137	benign	-0.47	Destabilizing	0.012	N	0.342	neutral	N	0.445562698	None	None	N
A/W	0.7149	likely_pathogenic	0.7672	pathogenic	-1.239	Destabilizing	0.864	D	0.619	neutral	None	None	None	None	N
A/Y	0.4181	ambiguous	0.4591	ambiguous	-0.892	Destabilizing	0.628	D	0.547	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.