TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7666	23221;23222;23223	chr2:178721023;178721022;178721021	chr2:179585750;179585749;179585748
N2AB	7349	22270;22271;22272	chr2:178721023;178721022;178721021	chr2:179585750;179585749;179585748
N2A	6422	19489;19490;19491	chr2:178721023;178721022;178721021	chr2:179585750;179585749;179585748
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-61
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.079
• 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	None	None	1.0	D	0.803	0.523	0.758381520966	gnomAD-4.0.0	1.36886E-06	None	None	None	None	N	None	5.97943E-05	0	None	0	0	None	0	0	0	0	0
L/V	rs2078276460	None	0.989	D	0.65	0.515	0.721660892059	gnomAD-4.0.0	6.84431E-07	None	None	None	None	N	None	0	0	None	0	2.51991E-05	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
L/A	0.9582	likely_pathogenic	0.9607	pathogenic	-2.715	Highly Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/C	0.9465	likely_pathogenic	0.9423	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.611	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
L/E	0.9974	likely_pathogenic	0.9983	pathogenic	-3.292	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/F	0.6107	likely_pathogenic	0.6612	pathogenic	-1.712	Destabilizing	1.0	D	0.803	deleterious	D	0.533713169	None	None	N
L/G	0.9937	likely_pathogenic	0.9949	pathogenic	-3.317	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/H	0.9912	likely_pathogenic	0.9938	pathogenic	-3.073	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.5833059	None	None	N
L/I	0.2208	likely_benign	0.2565	benign	-0.902	Destabilizing	0.985	D	0.64	neutral	N	0.5203554	None	None	N
L/K	0.995	likely_pathogenic	0.9968	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/M	0.3942	ambiguous	0.3958	ambiguous	-1.03	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
L/N	0.9976	likely_pathogenic	0.9983	pathogenic	-2.955	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
L/P	0.9976	likely_pathogenic	0.9987	pathogenic	-1.498	Destabilizing	1.0	D	0.905	deleterious	D	0.5833059	None	None	N
L/Q	0.985	likely_pathogenic	0.9887	pathogenic	-2.61	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/R	0.9874	likely_pathogenic	0.9917	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.5833059	None	None	N
L/S	0.9958	likely_pathogenic	0.9967	pathogenic	-3.489	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/T	0.986	likely_pathogenic	0.9892	pathogenic	-3.004	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
L/V	0.3215	likely_benign	0.3515	ambiguous	-1.498	Destabilizing	0.989	D	0.65	neutral	D	0.532156233	None	None	N
L/W	0.9659	likely_pathogenic	0.9749	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/Y	0.9717	likely_pathogenic	0.9782	pathogenic	-1.923	Destabilizing	0.998	D	0.856	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.