TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25131	75616;75617;75618	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
N2AB	23490	70693;70694;70695	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
N2A	22563	67912;67913;67914	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
N2B	16066	48421;48422;48423	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
Novex-1	16191	48796;48797;48798	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
Novex-2	16258	48997;48998;48999	chr2:178570741;178570740;178570739	chr2:179435468;179435467;179435466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-134
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.1279
• 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/F	None	None	0.055	N	0.626	0.206	0.154104182512	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79915E-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	0.3888	ambiguous	0.3852	ambiguous	-2.003	Highly Destabilizing	0.005	N	0.481	neutral	N	0.516839298	None	None	N
V/C	0.7539	likely_pathogenic	0.7604	pathogenic	-1.528	Destabilizing	0.628	D	0.734	prob.delet.	None	None	None	None	N
V/D	0.9606	likely_pathogenic	0.962	pathogenic	-2.383	Highly Destabilizing	0.295	N	0.783	deleterious	N	0.517012656	None	None	N
V/E	0.9295	likely_pathogenic	0.9334	pathogenic	-2.124	Highly Destabilizing	0.136	N	0.7	prob.neutral	None	None	None	None	N
V/F	0.2234	likely_benign	0.2342	benign	-1.259	Destabilizing	0.055	N	0.626	neutral	N	0.386957111	None	None	N
V/G	0.6782	likely_pathogenic	0.6869	pathogenic	-2.555	Highly Destabilizing	0.106	N	0.719	prob.delet.	N	0.517012656	None	None	N
V/H	0.9557	likely_pathogenic	0.9586	pathogenic	-2.195	Highly Destabilizing	0.864	D	0.823	deleterious	None	None	None	None	N
V/I	0.0596	likely_benign	0.0579	benign	-0.443	Destabilizing	None	N	0.227	neutral	N	0.353394403	None	None	N
V/K	0.9403	likely_pathogenic	0.9496	pathogenic	-1.602	Destabilizing	0.072	N	0.675	prob.neutral	None	None	None	None	N
V/L	0.0972	likely_benign	0.1032	benign	-0.443	Destabilizing	None	N	0.221	neutral	N	0.294161594	None	None	N
V/M	0.1301	likely_benign	0.1284	benign	-0.525	Destabilizing	0.001	N	0.381	neutral	None	None	None	None	N
V/N	0.8944	likely_pathogenic	0.8941	pathogenic	-2.03	Highly Destabilizing	0.356	N	0.78	deleterious	None	None	None	None	N
V/P	0.9261	likely_pathogenic	0.922	pathogenic	-0.939	Destabilizing	0.628	D	0.754	deleterious	None	None	None	None	N
V/Q	0.9234	likely_pathogenic	0.9294	pathogenic	-1.79	Destabilizing	0.356	N	0.752	deleterious	None	None	None	None	N
V/R	0.9069	likely_pathogenic	0.9179	pathogenic	-1.602	Destabilizing	0.214	N	0.783	deleterious	None	None	None	None	N
V/S	0.7662	likely_pathogenic	0.7593	pathogenic	-2.679	Highly Destabilizing	0.072	N	0.675	neutral	None	None	None	None	N
V/T	0.5626	ambiguous	0.5473	ambiguous	-2.251	Highly Destabilizing	0.031	N	0.534	neutral	None	None	None	None	N
V/W	0.8824	likely_pathogenic	0.8942	pathogenic	-1.666	Destabilizing	0.864	D	0.819	deleterious	None	None	None	None	N
V/Y	0.7669	likely_pathogenic	0.7883	pathogenic	-1.282	Destabilizing	0.356	N	0.715	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.