TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25004	75235;75236;75237	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
N2AB	23363	70312;70313;70314	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
N2A	22436	67531;67532;67533	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
N2B	15939	48040;48041;48042	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
Novex-1	16064	48415;48416;48417	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
Novex-2	16131	48616;48617;48618	chr2:178571122;178571121;178571120	chr2:179435849;179435848;179435847
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-69
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.6184
• 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
R/C	rs1320326326	-0.333	0.984	N	0.85	0.218	0.300784259202	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/C	rs1320326326	-0.333	0.984	N	0.85	0.218	0.300784259202	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs1320326326	-0.333	0.984	N	0.85	0.218	0.300784259202	gnomAD-4.0.0	6.19869E-06	None	None	None	None	N	None	5.34202E-05	1.66756E-05	None	0	0	None	0	0	3.39099E-06	1.09798E-05	0
R/G	rs1320326326	-0.765	0.249	N	0.533	0.143	0.251639045875	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
R/G	rs1320326326	-0.765	0.249	N	0.533	0.143	0.251639045875	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/G	rs1320326326	-0.765	0.249	N	0.533	0.143	0.251639045875	gnomAD-4.0.0	1.85961E-06	None	None	None	None	N	None	1.33551E-05	0	None	0	0	None	0	0	1.6955E-06	0	0
R/H	rs909041164	-1.062	0.002	N	0.202	0.185	0.233150807113	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
R/H	rs909041164	-1.062	0.002	N	0.202	0.185	0.233150807113	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
R/H	rs909041164	-1.062	0.002	N	0.202	0.185	0.233150807113	gnomAD-4.0.0	1.85961E-05	None	None	None	None	N	None	2.6713E-05	1.66744E-05	None	0	0	None	0	0	1.9498E-05	2.19616E-05	3.20318E-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
R/A	0.5442	ambiguous	0.559	ambiguous	-0.788	Destabilizing	0.147	N	0.541	neutral	None	None	None	None	N
R/C	0.1747	likely_benign	0.182	benign	-0.733	Destabilizing	0.984	D	0.85	deleterious	N	0.477276906	None	None	N
R/D	0.8851	likely_pathogenic	0.8938	pathogenic	-0.199	Destabilizing	0.378	N	0.559	neutral	None	None	None	None	N
R/E	0.5539	ambiguous	0.5745	pathogenic	-0.12	Destabilizing	0.08	N	0.471	neutral	None	None	None	None	N
R/F	0.6381	likely_pathogenic	0.6702	pathogenic	-0.903	Destabilizing	0.378	N	0.812	deleterious	None	None	None	None	N
R/G	0.4634	ambiguous	0.4728	ambiguous	-1.037	Destabilizing	0.249	N	0.533	neutral	N	0.513992915	None	None	N
R/H	0.1274	likely_benign	0.1362	benign	-1.336	Destabilizing	0.002	N	0.202	neutral	N	0.511256917	None	None	N
R/I	0.3608	ambiguous	0.3903	ambiguous	-0.139	Destabilizing	0.552	D	0.8	deleterious	None	None	None	None	N
R/K	0.1394	likely_benign	0.1407	benign	-0.835	Destabilizing	0.067	N	0.439	neutral	None	None	None	None	N
R/L	0.326	likely_benign	0.3434	ambiguous	-0.139	Destabilizing	0.249	N	0.504	neutral	N	0.519265449	None	None	N
R/M	0.3976	ambiguous	0.4148	ambiguous	-0.294	Destabilizing	0.934	D	0.561	neutral	None	None	None	None	N
R/N	0.7414	likely_pathogenic	0.7674	pathogenic	-0.239	Destabilizing	0.08	N	0.547	neutral	None	None	None	None	N
R/P	0.9656	likely_pathogenic	0.9679	pathogenic	-0.335	Destabilizing	0.702	D	0.827	deleterious	N	0.512395404	None	None	N
R/Q	0.1252	likely_benign	0.1235	benign	-0.524	Destabilizing	0.378	N	0.572	neutral	None	None	None	None	N
R/S	0.6446	likely_pathogenic	0.6618	pathogenic	-0.968	Destabilizing	0.249	N	0.563	neutral	N	0.464880189	None	None	N
R/T	0.388	ambiguous	0.4191	ambiguous	-0.737	Destabilizing	0.378	N	0.498	neutral	None	None	None	None	N
R/V	0.4167	ambiguous	0.4411	ambiguous	-0.335	Destabilizing	0.552	D	0.787	deleterious	None	None	None	None	N
R/W	0.2486	likely_benign	0.2624	benign	-0.628	Destabilizing	0.934	D	0.865	deleterious	None	None	None	None	N
R/Y	0.467	ambiguous	0.503	ambiguous	-0.3	Destabilizing	0.233	N	0.779	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.