TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25365	76318;76319;76320	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
N2AB	23724	71395;71396;71397	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
N2A	22797	68614;68615;68616	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
N2B	16300	49123;49124;49125	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
Novex-1	16425	49498;49499;49500	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
Novex-2	16492	49699;49700;49701	chr2:178570039;178570038;178570037	chr2:179434766;179434765;179434764
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-72
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.6221
• Predicted PPI site: I

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/G	None	None	0.008	N	0.391	0.184	0.421550847248	gnomAD-4.0.0	1.59223E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-05	0
R/K	None	None	0.008	N	0.227	0.073	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.8345	likely_pathogenic	0.8693	pathogenic	-0.366	Destabilizing	0.415	N	0.611	neutral	None	None	None	None	I
R/C	0.5121	ambiguous	0.5338	ambiguous	-0.418	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	I
R/D	0.956	likely_pathogenic	0.9678	pathogenic	0.028	Stabilizing	0.923	D	0.623	neutral	None	None	None	None	I
R/E	0.805	likely_pathogenic	0.8494	pathogenic	0.114	Stabilizing	0.633	D	0.573	neutral	None	None	None	None	I
R/F	0.917	likely_pathogenic	0.9239	pathogenic	-0.485	Destabilizing	0.987	D	0.694	prob.neutral	None	None	None	None	I
R/G	0.8021	likely_pathogenic	0.8405	pathogenic	-0.607	Destabilizing	0.008	N	0.391	neutral	N	0.478041055	None	None	I
R/H	0.2714	likely_benign	0.2857	benign	-1.017	Destabilizing	0.961	D	0.655	neutral	None	None	None	None	I
R/I	0.7205	likely_pathogenic	0.7666	pathogenic	0.248	Stabilizing	0.949	D	0.695	prob.neutral	N	0.464910323	None	None	I
R/K	0.1266	likely_benign	0.179	benign	-0.361	Destabilizing	0.008	N	0.227	neutral	N	0.424107203	None	None	I
R/L	0.6376	likely_pathogenic	0.6584	pathogenic	0.248	Stabilizing	0.775	D	0.623	neutral	None	None	None	None	I
R/M	0.6786	likely_pathogenic	0.7397	pathogenic	-0.095	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	I
R/N	0.9156	likely_pathogenic	0.9406	pathogenic	0.017	Stabilizing	0.775	D	0.609	neutral	None	None	None	None	I
R/P	0.8695	likely_pathogenic	0.8814	pathogenic	0.065	Stabilizing	0.961	D	0.707	prob.neutral	None	None	None	None	I
R/Q	0.286	likely_benign	0.3033	benign	-0.147	Destabilizing	0.858	D	0.633	neutral	None	None	None	None	I
R/S	0.9043	likely_pathogenic	0.9294	pathogenic	-0.57	Destabilizing	0.565	D	0.595	neutral	N	0.510379394	None	None	I
R/T	0.7037	likely_pathogenic	0.7721	pathogenic	-0.326	Destabilizing	0.722	D	0.625	neutral	N	0.444207543	None	None	I
R/V	0.7547	likely_pathogenic	0.7966	pathogenic	0.065	Stabilizing	0.923	D	0.665	neutral	None	None	None	None	I
R/W	0.5343	ambiguous	0.5231	ambiguous	-0.358	Destabilizing	0.996	D	0.719	prob.delet.	None	None	None	None	I
R/Y	0.8024	likely_pathogenic	0.8055	pathogenic	0.014	Stabilizing	0.987	D	0.7	prob.neutral	None	None	None	None	I

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.