TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8904	26935;26936;26937	chr2:178713948;178713947;178713946	chr2:179578675;179578674;179578673
N2AB	8587	25984;25985;25986	chr2:178713948;178713947;178713946	chr2:179578675;179578674;179578673
N2A	7660	23203;23204;23205	chr2:178713948;178713947;178713946	chr2:179578675;179578674;179578673
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-74
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0745
• 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	0.948	N	0.538	0.373	0.544738774389	gnomAD-4.0.0	6.84283E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99544E-07	0	0
V/M	None	None	0.998	N	0.773	0.484	0.612591404863	gnomAD-4.0.0	2.05285E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69863E-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	0.5505	ambiguous	0.5994	pathogenic	-2.329	Highly Destabilizing	0.994	D	0.608	neutral	N	0.388653409	None	None	N
V/C	0.9534	likely_pathogenic	0.9602	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/D	0.9933	likely_pathogenic	0.9923	pathogenic	-3.293	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/E	0.9822	likely_pathogenic	0.9799	pathogenic	-3.073	Highly Destabilizing	0.999	D	0.874	deleterious	D	0.538206166	None	None	N
V/F	0.8363	likely_pathogenic	0.829	pathogenic	-1.243	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	N
V/G	0.7423	likely_pathogenic	0.7623	pathogenic	-2.825	Highly Destabilizing	0.999	D	0.868	deleterious	N	0.496971226	None	None	N
V/H	0.9967	likely_pathogenic	0.9965	pathogenic	-2.388	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/I	0.1071	likely_benign	0.1037	benign	-0.929	Destabilizing	0.611	D	0.235	neutral	None	None	None	None	N
V/K	0.9909	likely_pathogenic	0.9895	pathogenic	-1.843	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/L	0.6068	likely_pathogenic	0.6109	pathogenic	-0.929	Destabilizing	0.948	D	0.538	neutral	N	0.493235017	None	None	N
V/M	0.6185	likely_pathogenic	0.6376	pathogenic	-1.372	Destabilizing	0.998	D	0.773	deleterious	N	0.515075481	None	None	N
V/N	0.9767	likely_pathogenic	0.9767	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9953	pathogenic	-1.373	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/Q	0.9845	likely_pathogenic	0.9836	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/R	0.9828	likely_pathogenic	0.9796	pathogenic	-1.666	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/S	0.8638	likely_pathogenic	0.8793	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/T	0.7619	likely_pathogenic	0.7786	pathogenic	-2.472	Highly Destabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	N
V/W	0.9972	likely_pathogenic	0.9976	pathogenic	-1.702	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/Y	0.9836	likely_pathogenic	0.9813	pathogenic	-1.434	Destabilizing	1.0	D	0.851	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.