TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2379	7360;7361;7362	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
N2AB	2379	7360;7361;7362	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
N2A	2379	7360;7361;7362	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
N2B	2333	7222;7223;7224	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
Novex-1	2333	7222;7223;7224	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
Novex-2	2333	7222;7223;7224	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758
Novex-3	2379	7360;7361;7362	chr2:178774033;178774032;178774031	chr2:179638760;179638759;179638758

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-13
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1361
• 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
V/L	None	None	0.002	D	0.319	0.235	0.289847578895	gnomAD-4.0.0	4.10452E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39586E-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
V/A	0.6722	likely_pathogenic	0.6869	pathogenic	-2.275	Highly Destabilizing	0.334	N	0.587	neutral	D	0.57442519	None	None	N
V/C	0.9043	likely_pathogenic	0.9061	pathogenic	-2.061	Highly Destabilizing	0.992	D	0.743	deleterious	None	None	None	None	N
V/D	0.9829	likely_pathogenic	0.9837	pathogenic	-3.074	Highly Destabilizing	0.963	D	0.811	deleterious	D	0.643127733	None	None	N
V/E	0.9697	likely_pathogenic	0.9727	pathogenic	-2.875	Highly Destabilizing	0.92	D	0.772	deleterious	None	None	None	None	N
V/F	0.3593	ambiguous	0.3724	ambiguous	-1.311	Destabilizing	0.002	N	0.41	neutral	D	0.54452863	None	None	N
V/G	0.7669	likely_pathogenic	0.7769	pathogenic	-2.786	Highly Destabilizing	0.896	D	0.769	deleterious	D	0.643127733	None	None	N
V/H	0.9839	likely_pathogenic	0.9849	pathogenic	-2.428	Highly Destabilizing	0.992	D	0.796	deleterious	None	None	None	None	N
V/I	0.1041	likely_benign	0.1108	benign	-0.85	Destabilizing	0.201	N	0.551	neutral	D	0.526641405	None	None	N
V/K	0.9836	likely_pathogenic	0.9846	pathogenic	-1.939	Destabilizing	0.92	D	0.769	deleterious	None	None	None	None	N
V/L	0.2357	likely_benign	0.2632	benign	-0.85	Destabilizing	0.002	N	0.319	neutral	D	0.53436259	None	None	N
V/M	0.3076	likely_benign	0.3342	benign	-1.077	Destabilizing	0.85	D	0.649	neutral	None	None	None	None	N
V/N	0.9501	likely_pathogenic	0.9545	pathogenic	-2.26	Highly Destabilizing	0.972	D	0.815	deleterious	None	None	None	None	N
V/P	0.9804	likely_pathogenic	0.9833	pathogenic	-1.3	Destabilizing	0.972	D	0.789	deleterious	None	None	None	None	N
V/Q	0.9691	likely_pathogenic	0.9722	pathogenic	-2.144	Highly Destabilizing	0.972	D	0.787	deleterious	None	None	None	None	N
V/R	0.9744	likely_pathogenic	0.9752	pathogenic	-1.683	Destabilizing	0.92	D	0.816	deleterious	None	None	None	None	N
V/S	0.8843	likely_pathogenic	0.8886	pathogenic	-2.847	Highly Destabilizing	0.766	D	0.751	deleterious	None	None	None	None	N
V/T	0.7137	likely_pathogenic	0.713	pathogenic	-2.514	Highly Destabilizing	0.617	D	0.629	neutral	None	None	None	None	N
V/W	0.9808	likely_pathogenic	0.9817	pathogenic	-1.801	Destabilizing	0.992	D	0.791	deleterious	None	None	None	None	N
V/Y	0.9123	likely_pathogenic	0.9157	pathogenic	-1.484	Destabilizing	0.447	N	0.709	prob.delet.	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.