TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33784	101575;101576;101577	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
N2AB	32143	96652;96653;96654	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
N2A	31216	93871;93872;93873	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
N2B	24719	74380;74381;74382	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
Novex-1	24844	74755;74756;74757	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
Novex-2	24911	74956;74957;74958	chr2:178535265;178535264;178535263	chr2:179399992;179399991;179399990
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-132
• Domain position: 96
• Structural Position: 132
• Q(SASA): 0.8699
• 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
E/Q	rs918368881	0.412	0.996	N	0.602	0.25	0.292062946507	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
E/Q	rs918368881	0.412	0.996	N	0.602	0.25	0.292062946507	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.31027E-04	0	0	0	None	0	0	0	0	0
E/Q	rs918368881	0.412	0.996	N	0.602	0.25	0.292062946507	gnomAD-4.0.0	1.31453E-05	None	None	None	None	N	None	0	1.31027E-04	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
E/A	0.5001	ambiguous	0.4507	ambiguous	-0.025	Destabilizing	0.983	D	0.627	neutral	N	0.451798024	None	None	N
E/C	0.986	likely_pathogenic	0.9857	pathogenic	-0.168	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	N
E/D	0.3814	ambiguous	0.3758	ambiguous	-0.229	Destabilizing	0.88	D	0.538	neutral	N	0.451798024	None	None	N
E/F	0.9718	likely_pathogenic	0.9675	pathogenic	-0.078	Destabilizing	0.999	D	0.657	prob.neutral	None	None	None	None	N
E/G	0.5472	ambiguous	0.5047	ambiguous	-0.14	Destabilizing	0.998	D	0.547	neutral	N	0.452838174	None	None	N
E/H	0.9516	likely_pathogenic	0.9466	pathogenic	0.51	Stabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/I	0.8434	likely_pathogenic	0.8132	pathogenic	0.22	Stabilizing	0.996	D	0.663	prob.neutral	None	None	None	None	N
E/K	0.7533	likely_pathogenic	0.6713	pathogenic	0.396	Stabilizing	0.991	D	0.627	neutral	N	0.45318489	None	None	N
E/L	0.8859	likely_pathogenic	0.8584	pathogenic	0.22	Stabilizing	0.996	D	0.601	neutral	None	None	None	None	N
E/M	0.8954	likely_pathogenic	0.8743	pathogenic	0.003	Stabilizing	0.994	D	0.711	prob.delet.	None	None	None	None	N
E/N	0.8129	likely_pathogenic	0.7929	pathogenic	0.221	Stabilizing	0.991	D	0.685	prob.delet.	None	None	None	None	N
E/P	0.8658	likely_pathogenic	0.838	pathogenic	0.156	Stabilizing	0.971	D	0.705	prob.delet.	None	None	None	None	N
E/Q	0.6249	likely_pathogenic	0.5785	pathogenic	0.224	Stabilizing	0.996	D	0.602	neutral	N	0.453358249	None	None	N
E/R	0.841	likely_pathogenic	0.8002	pathogenic	0.627	Stabilizing	0.998	D	0.69	prob.delet.	None	None	None	None	N
E/S	0.707	likely_pathogenic	0.6746	pathogenic	0.054	Stabilizing	0.987	D	0.664	prob.neutral	None	None	None	None	N
E/T	0.7165	likely_pathogenic	0.681	pathogenic	0.153	Stabilizing	0.997	D	0.696	prob.delet.	None	None	None	None	N
E/V	0.6736	likely_pathogenic	0.6244	pathogenic	0.156	Stabilizing	0.992	D	0.611	neutral	N	0.452664815	None	None	N
E/W	0.9906	likely_pathogenic	0.9888	pathogenic	-0.035	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/Y	0.9468	likely_pathogenic	0.9414	pathogenic	0.146	Stabilizing	1.0	D	0.679	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.