TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1128	3607;3608;3609	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
N2AB	1128	3607;3608;3609	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
N2A	1128	3607;3608;3609	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
N2B	1082	3469;3470;3471	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
Novex-1	1082	3469;3470;3471	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
Novex-2	1082	3469;3470;3471	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987
Novex-3	1128	3607;3608;3609	chr2:178781262;178781261;178781260	chr2:179645989;179645988;179645987

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-4
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1404
• 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
Y/C	None	None	1.0	D	0.816	0.756	0.772762111909	gnomAD-4.0.0	1.59113E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85732E-06	0	0
Y/H	None	None	1.0	N	0.715	0.682	0.519024713989	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
Y/A	0.9674	likely_pathogenic	0.9541	pathogenic	-2.769	Highly Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
Y/C	0.568	likely_pathogenic	0.4897	ambiguous	-2.068	Highly Destabilizing	1.0	D	0.816	deleterious	D	0.589492175	None	None	N
Y/D	0.9715	likely_pathogenic	0.9665	pathogenic	-1.982	Destabilizing	1.0	D	0.848	deleterious	N	0.514231533	None	None	N
Y/E	0.9821	likely_pathogenic	0.9756	pathogenic	-1.798	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
Y/F	0.2836	likely_benign	0.2523	benign	-1.104	Destabilizing	0.999	D	0.511	neutral	N	0.465006975	None	None	N
Y/G	0.95	likely_pathogenic	0.9337	pathogenic	-3.185	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
Y/H	0.4895	ambiguous	0.4972	ambiguous	-1.744	Destabilizing	1.0	D	0.715	prob.delet.	N	0.50283256	None	None	N
Y/I	0.9281	likely_pathogenic	0.8857	pathogenic	-1.432	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
Y/K	0.9809	likely_pathogenic	0.9668	pathogenic	-1.939	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
Y/L	0.862	likely_pathogenic	0.8196	pathogenic	-1.432	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
Y/M	0.9472	likely_pathogenic	0.9244	pathogenic	-1.407	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
Y/N	0.7565	likely_pathogenic	0.7482	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.572357716	None	None	N
Y/P	0.9957	likely_pathogenic	0.9953	pathogenic	-1.884	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/Q	0.9492	likely_pathogenic	0.9331	pathogenic	-2.28	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
Y/R	0.9432	likely_pathogenic	0.9173	pathogenic	-1.7	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/S	0.8617	likely_pathogenic	0.8344	pathogenic	-3.134	Highly Destabilizing	1.0	D	0.793	deleterious	N	0.515972074	None	None	N
Y/T	0.946	likely_pathogenic	0.9248	pathogenic	-2.825	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
Y/V	0.8618	likely_pathogenic	0.7944	pathogenic	-1.884	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
Y/W	0.7405	likely_pathogenic	0.7211	pathogenic	-0.464	Destabilizing	1.0	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.