TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29499	88720;88721;88722	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
N2AB	27858	83797;83798;83799	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
N2A	26931	81016;81017;81018	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
N2B	20434	61525;61526;61527	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
Novex-1	20559	61900;61901;61902	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
Novex-2	20626	62101;62102;62103	chr2:178554964;178554963;178554962	chr2:179419691;179419690;179419689
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-146
• Domain position: 56
• Structural Position: 139
• Q(SASA): 0.2741
• 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
L/F	rs968816753	None	0.007	N	0.299	0.142	0.422762650823	gnomAD-4.0.0	1.59147E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85804E-06	0	0
L/R	rs72648234	-0.882	0.939	N	0.564	0.433	None	gnomAD-2.1.1	1.42956E-04	None	None	None	None	N	None	4.13E-05	0	None	0	0	None	0	None	0	3.04983E-04	0
L/R	rs72648234	-0.882	0.939	N	0.564	0.433	None	gnomAD-3.1.2	9.2E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.76382E-04	0	0
L/R	rs72648234	-0.882	0.939	N	0.564	0.433	None	gnomAD-4.0.0	1.56789E-04	None	None	None	None	N	None	4.00481E-05	0	None	0	0	None	1.56294E-05	0	2.0342E-04	0	1.44125E-04

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
L/A	0.1712	likely_benign	0.1755	benign	-2.114	Highly Destabilizing	0.373	N	0.503	neutral	None	None	None	None	N
L/C	0.3133	likely_benign	0.3092	benign	-1.522	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	N
L/D	0.535	ambiguous	0.515	ambiguous	-1.721	Destabilizing	0.91	D	0.591	neutral	None	None	None	None	N
L/E	0.2767	likely_benign	0.26	benign	-1.662	Destabilizing	0.91	D	0.579	neutral	None	None	None	None	N
L/F	0.0858	likely_benign	0.085	benign	-1.379	Destabilizing	0.007	N	0.299	neutral	N	0.430836466	None	None	N
L/G	0.5097	ambiguous	0.502	ambiguous	-2.496	Highly Destabilizing	0.742	D	0.564	neutral	None	None	None	None	N
L/H	0.1146	likely_benign	0.1163	benign	-1.609	Destabilizing	0.994	D	0.592	neutral	N	0.487383183	None	None	N
L/I	0.0644	likely_benign	0.0667	benign	-1.095	Destabilizing	0.007	N	0.391	neutral	N	0.429969675	None	None	N
L/K	0.2578	likely_benign	0.2412	benign	-1.483	Destabilizing	0.91	D	0.561	neutral	None	None	None	None	N
L/M	0.085	likely_benign	0.0873	benign	-0.989	Destabilizing	0.91	D	0.543	neutral	None	None	None	None	N
L/N	0.2504	likely_benign	0.2589	benign	-1.405	Destabilizing	0.91	D	0.592	neutral	None	None	None	None	N
L/P	0.9459	likely_pathogenic	0.9282	pathogenic	-1.407	Destabilizing	0.939	D	0.588	neutral	N	0.517186015	None	None	N
L/Q	0.1066	likely_benign	0.1088	benign	-1.552	Destabilizing	0.953	D	0.562	neutral	None	None	None	None	N
L/R	0.1698	likely_benign	0.1564	benign	-0.903	Destabilizing	0.939	D	0.564	neutral	N	0.431180396	None	None	N
L/S	0.1672	likely_benign	0.1683	benign	-2.111	Highly Destabilizing	0.101	N	0.455	neutral	None	None	None	None	N
L/T	0.1097	likely_benign	0.1139	benign	-1.933	Destabilizing	0.59	D	0.48	neutral	None	None	None	None	N
L/V	0.0662	likely_benign	0.0677	benign	-1.407	Destabilizing	0.134	N	0.551	neutral	N	0.416944449	None	None	N
L/W	0.1896	likely_benign	0.1815	benign	-1.462	Destabilizing	0.996	D	0.569	neutral	None	None	None	None	N
L/Y	0.2338	likely_benign	0.2252	benign	-1.257	Destabilizing	0.835	D	0.539	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.