TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27606	83041;83042;83043	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
N2AB	25965	78118;78119;78120	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
N2A	25038	75337;75338;75339	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
N2B	18541	55846;55847;55848	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
Novex-1	18666	56221;56222;56223	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
Novex-2	18733	56422;56423;56424	chr2:178563316;178563315;178563314	chr2:179428043;179428042;179428041
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: Fn3-89
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.3026
• 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/A	rs1395661220	-1.88	0.822	N	0.605	0.297	0.632854968478	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/I	rs777713575	-0.319	0.006	N	0.243	0.038	0.288352970974	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	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	0.2653	likely_benign	0.2709	benign	-2.058	Highly Destabilizing	0.822	D	0.605	neutral	N	0.501933269	None	None	N
V/C	0.6452	likely_pathogenic	0.6799	pathogenic	-1.943	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
V/D	0.7398	likely_pathogenic	0.7256	pathogenic	-2.534	Highly Destabilizing	0.99	D	0.775	deleterious	N	0.52061503	None	None	N
V/E	0.5055	ambiguous	0.5205	ambiguous	-2.382	Highly Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
V/F	0.1703	likely_benign	0.1946	benign	-1.286	Destabilizing	0.942	D	0.694	prob.neutral	N	0.499933113	None	None	N
V/G	0.5123	ambiguous	0.4883	ambiguous	-2.52	Highly Destabilizing	0.971	D	0.754	deleterious	N	0.494575148	None	None	N
V/H	0.6017	likely_pathogenic	0.6524	pathogenic	-2.055	Highly Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
V/I	0.061	likely_benign	0.0662	benign	-0.801	Destabilizing	0.006	N	0.243	neutral	N	0.391477497	None	None	N
V/K	0.4705	ambiguous	0.4994	ambiguous	-1.665	Destabilizing	0.978	D	0.721	prob.delet.	None	None	None	None	N
V/L	0.1227	likely_benign	0.1542	benign	-0.801	Destabilizing	0.247	N	0.469	neutral	N	0.441962245	None	None	N
V/M	0.1032	likely_benign	0.1244	benign	-1.047	Destabilizing	0.956	D	0.687	prob.neutral	None	None	None	None	N
V/N	0.4803	ambiguous	0.5233	ambiguous	-1.862	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
V/P	0.9799	likely_pathogenic	0.9774	pathogenic	-1.191	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
V/Q	0.4229	ambiguous	0.463	ambiguous	-1.842	Destabilizing	0.993	D	0.742	deleterious	None	None	None	None	N
V/R	0.3664	ambiguous	0.3912	ambiguous	-1.36	Destabilizing	0.993	D	0.776	deleterious	None	None	None	None	N
V/S	0.3334	likely_benign	0.3388	benign	-2.487	Highly Destabilizing	0.978	D	0.71	prob.delet.	None	None	None	None	N
V/T	0.2016	likely_benign	0.2174	benign	-2.204	Highly Destabilizing	0.86	D	0.63	neutral	None	None	None	None	N
V/W	0.7394	likely_pathogenic	0.777	pathogenic	-1.639	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
V/Y	0.5203	ambiguous	0.558	ambiguous	-1.309	Destabilizing	0.978	D	0.705	prob.neutral	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.