TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27860	83803;83804;83805	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
N2AB	26219	78880;78881;78882	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
N2A	25292	76099;76100;76101	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
N2B	18795	56608;56609;56610	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
Novex-1	18920	56983;56984;56985	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
Novex-2	18987	57184;57185;57186	chr2:178562554;178562553;178562552	chr2:179427281;179427280;179427279
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: Fn3-90
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.0625
• 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	None	None	None	N	0.369	0.086	0.112648838833	gnomAD-4.0.0	1.60069E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86885E-06	0	0
V/L	None	None	0.026	N	0.522	0.108	0.294918367191	gnomAD-4.0.0	3.19862E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.73549E-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	0.176	likely_benign	0.159	benign	-2.311	Highly Destabilizing	None	N	0.369	neutral	N	0.398187251	None	None	N
V/C	0.838	likely_pathogenic	0.8137	pathogenic	-2.36	Highly Destabilizing	0.823	D	0.674	prob.neutral	None	None	None	None	N
V/D	0.9756	likely_pathogenic	0.9762	pathogenic	-3.162	Highly Destabilizing	0.378	N	0.809	deleterious	None	None	None	None	N
V/E	0.9671	likely_pathogenic	0.9658	pathogenic	-2.982	Highly Destabilizing	0.314	N	0.7	prob.delet.	N	0.475667063	None	None	N
V/F	0.7566	likely_pathogenic	0.7464	pathogenic	-1.408	Destabilizing	0.552	D	0.692	prob.delet.	None	None	None	None	N
V/G	0.528	ambiguous	0.5196	ambiguous	-2.785	Highly Destabilizing	0.061	N	0.765	deleterious	N	0.490540052	None	None	N
V/H	0.988	likely_pathogenic	0.9869	pathogenic	-2.247	Highly Destabilizing	0.934	D	0.793	deleterious	None	None	None	None	N
V/I	0.1232	likely_benign	0.1114	benign	-0.998	Destabilizing	0.002	N	0.327	neutral	None	None	None	None	N
V/K	0.9829	likely_pathogenic	0.9834	pathogenic	-1.902	Destabilizing	0.378	N	0.711	prob.delet.	None	None	None	None	N
V/L	0.5612	ambiguous	0.5119	ambiguous	-0.998	Destabilizing	0.026	N	0.522	neutral	N	0.452845669	None	None	N
V/M	0.5111	ambiguous	0.4886	ambiguous	-1.362	Destabilizing	0.481	N	0.599	neutral	N	0.461083937	None	None	N
V/N	0.8796	likely_pathogenic	0.8783	pathogenic	-2.244	Highly Destabilizing	0.552	D	0.797	deleterious	None	None	None	None	N
V/P	0.6966	likely_pathogenic	0.6931	pathogenic	-1.41	Destabilizing	0.378	N	0.744	deleterious	None	None	None	None	N
V/Q	0.959	likely_pathogenic	0.9579	pathogenic	-2.19	Highly Destabilizing	0.552	D	0.725	deleterious	None	None	None	None	N
V/R	0.9664	likely_pathogenic	0.9677	pathogenic	-1.586	Destabilizing	0.378	N	0.801	deleterious	None	None	None	None	N
V/S	0.4921	ambiguous	0.4676	ambiguous	-2.831	Highly Destabilizing	0.08	N	0.696	prob.delet.	None	None	None	None	N
V/T	0.4469	ambiguous	0.3908	ambiguous	-2.52	Highly Destabilizing	0.08	N	0.585	neutral	None	None	None	None	N
V/W	0.9942	likely_pathogenic	0.9939	pathogenic	-1.786	Destabilizing	0.934	D	0.743	deleterious	None	None	None	None	N
V/Y	0.9675	likely_pathogenic	0.9674	pathogenic	-1.498	Destabilizing	0.552	D	0.664	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.