TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27762	83509;83510;83511	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
N2AB	26121	78586;78587;78588	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
N2A	25194	75805;75806;75807	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
N2B	18697	56314;56315;56316	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
Novex-1	18822	56689;56690;56691	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
Novex-2	18889	56890;56891;56892	chr2:178562848;178562847;178562846	chr2:179427575;179427574;179427573
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: Ig-141
• Domain position: 87
• Structural Position: 175
• Q(SASA): 0.67
• 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/T	rs562523414	-0.297	0.822	N	0.611	0.286	0.436348499334	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
R/T	rs562523414	-0.297	0.822	N	0.611	0.286	0.436348499334	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/T	rs562523414	-0.297	0.822	N	0.611	0.286	0.436348499334	gnomAD-4.0.0	4.0596E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.87917E-04	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	0.9333	likely_pathogenic	0.9221	pathogenic	-0.515	Destabilizing	0.754	D	0.609	neutral	None	None	None	None	I
R/C	0.6225	likely_pathogenic	0.5749	pathogenic	-0.564	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
R/D	0.9804	likely_pathogenic	0.9761	pathogenic	0.127	Stabilizing	0.956	D	0.634	neutral	None	None	None	None	I
R/E	0.8962	likely_pathogenic	0.8782	pathogenic	0.247	Stabilizing	0.754	D	0.581	neutral	None	None	None	None	I
R/F	0.9626	likely_pathogenic	0.9509	pathogenic	-0.424	Destabilizing	0.993	D	0.723	prob.delet.	None	None	None	None	I
R/G	0.9281	likely_pathogenic	0.9147	pathogenic	-0.803	Destabilizing	0.822	D	0.607	neutral	N	0.502987344	None	None	I
R/H	0.3444	ambiguous	0.287	benign	-1.132	Destabilizing	0.978	D	0.581	neutral	None	None	None	None	I
R/I	0.7784	likely_pathogenic	0.7565	pathogenic	0.245	Stabilizing	0.97	D	0.726	prob.delet.	N	0.506448946	None	None	I
R/K	0.1715	likely_benign	0.1453	benign	-0.46	Destabilizing	0.006	N	0.243	neutral	N	0.417192379	None	None	I
R/L	0.7525	likely_pathogenic	0.7271	pathogenic	0.245	Stabilizing	0.86	D	0.607	neutral	None	None	None	None	I
R/M	0.7991	likely_pathogenic	0.764	pathogenic	-0.211	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
R/N	0.9542	likely_pathogenic	0.9387	pathogenic	-0.101	Destabilizing	0.956	D	0.583	neutral	None	None	None	None	I
R/P	0.9952	likely_pathogenic	0.9958	pathogenic	0.013	Stabilizing	0.978	D	0.713	prob.delet.	None	None	None	None	I
R/Q	0.3311	likely_benign	0.2886	benign	-0.209	Destabilizing	0.956	D	0.616	neutral	None	None	None	None	I
R/S	0.9512	likely_pathogenic	0.9333	pathogenic	-0.779	Destabilizing	0.822	D	0.626	neutral	N	0.493461006	None	None	I
R/T	0.816	likely_pathogenic	0.7741	pathogenic	-0.48	Destabilizing	0.822	D	0.611	neutral	N	0.494498369	None	None	I
R/V	0.83	likely_pathogenic	0.8086	pathogenic	0.013	Stabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	I
R/W	0.7127	likely_pathogenic	0.673	pathogenic	-0.198	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
R/Y	0.8944	likely_pathogenic	0.8639	pathogenic	0.129	Stabilizing	0.993	D	0.715	prob.delet.	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.