TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28035	84328;84329;84330	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
N2AB	26394	79405;79406;79407	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
N2A	25467	76624;76625;76626	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
N2B	18970	57133;57134;57135	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
Novex-1	19095	57508;57509;57510	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
Novex-2	19162	57709;57710;57711	chr2:178562029;178562028;178562027	chr2:179426756;179426755;179426754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-142
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.1033
• 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
L/F	rs878854394	-1.806	0.901	N	0.745	0.147	0.298403945805	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
L/F	rs878854394	-1.806	0.901	N	0.745	0.147	0.298403945805	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs878854394	-1.806	0.901	N	0.745	0.147	0.298403945805	gnomAD-4.0.0	4.95861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78136E-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
L/A	0.8192	likely_pathogenic	0.8653	pathogenic	-2.984	Highly Destabilizing	0.415	N	0.769	deleterious	None	None	None	None	N
L/C	0.8071	likely_pathogenic	0.8279	pathogenic	-2.378	Highly Destabilizing	0.989	D	0.787	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9989	pathogenic	-3.805	Highly Destabilizing	0.987	D	0.861	deleterious	None	None	None	None	N
L/E	0.9921	likely_pathogenic	0.9946	pathogenic	-3.511	Highly Destabilizing	0.961	D	0.86	deleterious	None	None	None	None	N
L/F	0.5211	ambiguous	0.5188	ambiguous	-1.839	Destabilizing	0.901	D	0.745	deleterious	N	0.511485754	None	None	N
L/G	0.97	likely_pathogenic	0.9803	pathogenic	-3.586	Highly Destabilizing	0.961	D	0.852	deleterious	None	None	None	None	N
L/H	0.9806	likely_pathogenic	0.9853	pathogenic	-3.163	Highly Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	N
L/I	0.0886	likely_benign	0.0809	benign	-1.187	Destabilizing	0.003	N	0.389	neutral	N	0.374784743	None	None	N
L/K	0.9874	likely_pathogenic	0.9898	pathogenic	-2.561	Highly Destabilizing	0.961	D	0.831	deleterious	None	None	None	None	N
L/M	0.2514	likely_benign	0.2479	benign	-1.194	Destabilizing	0.923	D	0.711	prob.delet.	None	None	None	None	N
L/N	0.9891	likely_pathogenic	0.9918	pathogenic	-3.152	Highly Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
L/P	0.975	likely_pathogenic	0.9838	pathogenic	-1.774	Destabilizing	0.987	D	0.859	deleterious	None	None	None	None	N
L/Q	0.9733	likely_pathogenic	0.9814	pathogenic	-2.898	Highly Destabilizing	0.987	D	0.829	deleterious	None	None	None	None	N
L/R	0.9736	likely_pathogenic	0.9813	pathogenic	-2.385	Highly Destabilizing	0.961	D	0.835	deleterious	None	None	None	None	N
L/S	0.9804	likely_pathogenic	0.9873	pathogenic	-3.776	Highly Destabilizing	0.901	D	0.829	deleterious	N	0.46249297	None	None	N
L/T	0.9151	likely_pathogenic	0.9373	pathogenic	-3.322	Highly Destabilizing	0.775	D	0.803	deleterious	None	None	None	None	N
L/V	0.1094	likely_benign	0.1164	benign	-1.774	Destabilizing	0.003	N	0.392	neutral	N	0.396986812	None	None	N
L/W	0.9341	likely_pathogenic	0.9437	pathogenic	-2.312	Highly Destabilizing	0.996	D	0.834	deleterious	None	None	None	None	N
L/Y	0.92	likely_pathogenic	0.9284	pathogenic	-2.065	Highly Destabilizing	0.961	D	0.791	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.