TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24593	74002;74003;74004	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
N2AB	22952	69079;69080;69081	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
N2A	22025	66298;66299;66300	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
N2B	15528	46807;46808;46809	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
Novex-1	15653	47182;47183;47184	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
Novex-2	15720	47383;47384;47385	chr2:178572355;178572354;178572353	chr2:179437082;179437081;179437080
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: Fn3-66
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0803
• 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	None	None	0.29	N	0.189	0.35	0.581280949539	gnomAD-4.0.0	1.59448E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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	0.9613	likely_pathogenic	0.9206	pathogenic	-2.741	Highly Destabilizing	0.987	D	0.547	neutral	D	0.566304509	None	None	N
V/C	0.9765	likely_pathogenic	0.9625	pathogenic	-2.185	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9992	pathogenic	-3.777	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.659897235	None	None	N
V/E	0.9985	likely_pathogenic	0.9974	pathogenic	-3.475	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/F	0.9665	likely_pathogenic	0.9254	pathogenic	-1.649	Destabilizing	1.0	D	0.715	prob.delet.	D	0.589181704	None	None	N
V/G	0.9804	likely_pathogenic	0.9611	pathogenic	-3.299	Highly Destabilizing	1.0	D	0.866	deleterious	D	0.659897235	None	None	N
V/H	0.9996	likely_pathogenic	0.9991	pathogenic	-3.051	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/I	0.1168	likely_benign	0.0993	benign	-1.094	Destabilizing	0.29	N	0.189	neutral	N	0.496411341	None	None	N
V/K	0.9989	likely_pathogenic	0.9981	pathogenic	-2.471	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/L	0.8094	likely_pathogenic	0.7014	pathogenic	-1.094	Destabilizing	0.853	D	0.245	neutral	D	0.528673513	None	None	N
V/M	0.9213	likely_pathogenic	0.8372	pathogenic	-1.284	Destabilizing	1.0	D	0.61	neutral	None	None	None	None	N
V/N	0.9977	likely_pathogenic	0.9958	pathogenic	-3.139	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9983	likely_pathogenic	0.997	pathogenic	-1.629	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9984	likely_pathogenic	0.9968	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/R	0.9975	likely_pathogenic	0.9958	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/S	0.9904	likely_pathogenic	0.9803	pathogenic	-3.611	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/T	0.9722	likely_pathogenic	0.9543	pathogenic	-3.169	Highly Destabilizing	1.0	D	0.569	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9992	pathogenic	-2.195	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9977	likely_pathogenic	0.9948	pathogenic	-1.949	Destabilizing	1.0	D	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.