TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8639	26140;26141;26142	chr2:178715499;178715498;178715497	chr2:179580226;179580225;179580224
N2AB	8322	25189;25190;25191	chr2:178715499;178715498;178715497	chr2:179580226;179580225;179580224
N2A	7395	22408;22409;22410	chr2:178715499;178715498;178715497	chr2:179580226;179580225;179580224
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-71
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.5142
• 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/I	rs1427227571	None	0.012	N	0.481	0.369	0.430239905395	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
V/I	rs1427227571	None	0.012	N	0.481	0.369	0.430239905395	gnomAD-4.0.0	1.371E-06	None	None	None	None	N	None	0	0	None	0	2.52283E-05	None	0	0	9.01115E-07	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	0.7901	likely_pathogenic	0.7014	pathogenic	-2.091	Highly Destabilizing	0.974	D	0.648	neutral	D	0.643824282	None	None	N
V/C	0.973	likely_pathogenic	0.9613	pathogenic	-1.979	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
V/D	0.996	likely_pathogenic	0.9901	pathogenic	-2.592	Highly Destabilizing	1.0	D	0.731	prob.delet.	D	0.644429695	None	None	N
V/E	0.9858	likely_pathogenic	0.9679	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/F	0.8855	likely_pathogenic	0.8193	pathogenic	-1.394	Destabilizing	0.999	D	0.721	prob.delet.	D	0.643824282	None	None	N
V/G	0.8574	likely_pathogenic	0.7731	pathogenic	-2.508	Highly Destabilizing	1.0	D	0.71	prob.delet.	D	0.644429695	None	None	N
V/H	0.997	likely_pathogenic	0.9934	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/I	0.1162	likely_benign	0.1106	benign	-0.971	Destabilizing	0.012	N	0.481	neutral	N	0.508713288	None	None	N
V/K	0.9926	likely_pathogenic	0.9823	pathogenic	-1.741	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/L	0.7605	likely_pathogenic	0.6608	pathogenic	-0.971	Destabilizing	0.753	D	0.66	neutral	D	0.609535353	None	None	N
V/M	0.7491	likely_pathogenic	0.6377	pathogenic	-1.156	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
V/N	0.9815	likely_pathogenic	0.9581	pathogenic	-1.886	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
V/P	0.9777	likely_pathogenic	0.9668	pathogenic	-1.316	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
V/Q	0.9876	likely_pathogenic	0.973	pathogenic	-1.923	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/R	0.9866	likely_pathogenic	0.9701	pathogenic	-1.359	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
V/S	0.9363	likely_pathogenic	0.8842	pathogenic	-2.475	Highly Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
V/T	0.8733	likely_pathogenic	0.7892	pathogenic	-2.233	Highly Destabilizing	0.976	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.9975	likely_pathogenic	0.9945	pathogenic	-1.701	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/Y	0.987	likely_pathogenic	0.974	pathogenic	-1.399	Destabilizing	0.999	D	0.727	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.