TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8880	26863;26864;26865	chr2:178714020;178714019;178714018	chr2:179578747;179578746;179578745
N2AB	8563	25912;25913;25914	chr2:178714020;178714019;178714018	chr2:179578747;179578746;179578745
N2A	7636	23131;23132;23133	chr2:178714020;178714019;178714018	chr2:179578747;179578746;179578745
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-74
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.3837
• 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
F/C	rs397517518	None	1.0	N	0.779	0.48	0.765860160457	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
F/C	rs397517518	None	1.0	N	0.779	0.48	0.765860160457	gnomAD-4.0.0	2.54114E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39076E-05	0	1.60169E-05

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
F/A	0.7974	likely_pathogenic	0.8411	pathogenic	-1.809	Destabilizing	0.992	D	0.689	prob.neutral	None	None	None	None	N
F/C	0.4877	ambiguous	0.6355	pathogenic	-1.091	Destabilizing	1.0	D	0.779	deleterious	N	0.485301163	None	None	N
F/D	0.9334	likely_pathogenic	0.9414	pathogenic	0.165	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
F/E	0.9571	likely_pathogenic	0.9605	pathogenic	0.266	Stabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
F/G	0.9216	likely_pathogenic	0.9369	pathogenic	-2.138	Highly Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
F/H	0.7259	likely_pathogenic	0.7646	pathogenic	-0.414	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
F/I	0.2798	likely_benign	0.3426	ambiguous	-0.841	Destabilizing	0.989	D	0.705	prob.neutral	N	0.504467433	None	None	N
F/K	0.9486	likely_pathogenic	0.9585	pathogenic	-0.886	Destabilizing	0.999	D	0.788	deleterious	None	None	None	None	N
F/L	0.8583	likely_pathogenic	0.9006	pathogenic	-0.841	Destabilizing	0.989	D	0.657	neutral	N	0.48436152	None	None	N
F/M	0.6465	likely_pathogenic	0.7119	pathogenic	-0.732	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
F/N	0.7786	likely_pathogenic	0.8226	pathogenic	-0.96	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
F/P	0.9945	likely_pathogenic	0.9966	pathogenic	-1.154	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
F/Q	0.9095	likely_pathogenic	0.9231	pathogenic	-0.934	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
F/R	0.8683	likely_pathogenic	0.8948	pathogenic	-0.389	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
F/S	0.5813	likely_pathogenic	0.6628	pathogenic	-1.872	Destabilizing	0.978	D	0.711	prob.delet.	N	0.441013388	None	None	N
F/T	0.6747	likely_pathogenic	0.7347	pathogenic	-1.676	Destabilizing	0.611	D	0.507	neutral	None	None	None	None	N
F/V	0.2769	likely_benign	0.3292	benign	-1.154	Destabilizing	0.989	D	0.714	prob.delet.	N	0.45586541	None	None	N
F/W	0.7058	likely_pathogenic	0.7527	pathogenic	0.054	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
F/Y	0.1999	likely_benign	0.2246	benign	-0.175	Destabilizing	0.998	D	0.664	neutral	N	0.485996316	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.