TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14026	42301;42302;42303	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
N2AB	12385	37378;37379;37380	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
N2A	11458	34597;34598;34599	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
N2B	4961	15106;15107;15108	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
Novex-1	5086	15481;15482;15483	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
Novex-2	5153	15682;15683;15684	chr2:178634798;178634797;178634796	chr2:179499525;179499524;179499523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-90
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0954
• 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	0.994	N	0.607	0.34	0.432493127443	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
V/A	0.8875	likely_pathogenic	0.8757	pathogenic	-2.256	Highly Destabilizing	0.997	D	0.599	neutral	N	0.437547429	None	None	N
V/C	0.9589	likely_pathogenic	0.9623	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/D	0.9972	likely_pathogenic	0.9971	pathogenic	-2.897	Highly Destabilizing	0.999	D	0.863	deleterious	D	0.526813242	None	None	N
V/E	0.9932	likely_pathogenic	0.9924	pathogenic	-2.758	Highly Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
V/F	0.9855	likely_pathogenic	0.9744	pathogenic	-1.448	Destabilizing	0.999	D	0.86	deleterious	D	0.523832949	None	None	N
V/G	0.911	likely_pathogenic	0.9116	pathogenic	-2.7	Highly Destabilizing	0.999	D	0.864	deleterious	D	0.525795783	None	None	N
V/H	0.9991	likely_pathogenic	0.999	pathogenic	-2.184	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/I	0.3422	ambiguous	0.2501	benign	-1.046	Destabilizing	0.994	D	0.575	neutral	N	0.518725445	None	None	N
V/K	0.9967	likely_pathogenic	0.9958	pathogenic	-1.884	Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
V/L	0.8906	likely_pathogenic	0.8228	pathogenic	-1.046	Destabilizing	0.994	D	0.607	neutral	N	0.440066757	None	None	N
V/M	0.9262	likely_pathogenic	0.8929	pathogenic	-1.168	Destabilizing	0.999	D	0.735	deleterious	None	None	None	None	N
V/N	0.987	likely_pathogenic	0.9874	pathogenic	-2.076	Highly Destabilizing	0.999	D	0.84	deleterious	None	None	None	None	N
V/P	0.9888	likely_pathogenic	0.9787	pathogenic	-1.423	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9933	likely_pathogenic	0.9932	pathogenic	-2.082	Highly Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/R	0.9938	likely_pathogenic	0.9925	pathogenic	-1.491	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/S	0.9688	likely_pathogenic	0.9724	pathogenic	-2.658	Highly Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/T	0.8859	likely_pathogenic	0.8907	pathogenic	-2.398	Highly Destabilizing	0.998	D	0.554	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9996	pathogenic	-1.81	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/Y	0.9977	likely_pathogenic	0.9967	pathogenic	-1.523	Destabilizing	0.999	D	0.839	deleterious	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.