TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5969	18130;18131;18132	chr2:178730628;178730627;178730626	chr2:179595355;179595354;179595353
N2AB	5652	17179;17180;17181	chr2:178730628;178730627;178730626	chr2:179595355;179595354;179595353
N2A	4725	14398;14399;14400	chr2:178730628;178730627;178730626	chr2:179595355;179595354;179595353
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-43
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.302
• 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/S	rs1480885716	-1.931	1.0	N	0.811	0.48	0.762273904298	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
F/S	rs1480885716	-1.931	1.0	N	0.811	0.48	0.762273904298	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	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
F/A	0.9548	likely_pathogenic	0.9599	pathogenic	-2.34	Highly Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
F/C	0.8001	likely_pathogenic	0.7983	pathogenic	-1.092	Destabilizing	1.0	D	0.835	deleterious	D	0.531211318	None	None	N
F/D	0.9889	likely_pathogenic	0.99	pathogenic	-1.29	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
F/E	0.9877	likely_pathogenic	0.9893	pathogenic	-1.204	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
F/G	0.9827	likely_pathogenic	0.9834	pathogenic	-2.69	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
F/H	0.9074	likely_pathogenic	0.9152	pathogenic	-1.01	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
F/I	0.6298	likely_pathogenic	0.6334	pathogenic	-1.279	Destabilizing	1.0	D	0.776	deleterious	N	0.509854611	None	None	N
F/K	0.984	likely_pathogenic	0.9861	pathogenic	-1.249	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
F/L	0.9579	likely_pathogenic	0.9545	pathogenic	-1.279	Destabilizing	0.999	D	0.689	prob.neutral	N	0.464698324	None	None	N
F/M	0.8374	likely_pathogenic	0.8316	pathogenic	-0.844	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
F/N	0.9532	likely_pathogenic	0.958	pathogenic	-1.28	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
F/P	0.9991	likely_pathogenic	0.9992	pathogenic	-1.628	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
F/Q	0.9661	likely_pathogenic	0.9713	pathogenic	-1.388	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
F/R	0.9592	likely_pathogenic	0.9649	pathogenic	-0.559	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
F/S	0.9054	likely_pathogenic	0.9153	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.811	deleterious	N	0.505390153	None	None	N
F/T	0.9265	likely_pathogenic	0.9347	pathogenic	-1.885	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/V	0.6371	likely_pathogenic	0.6384	pathogenic	-1.628	Destabilizing	1.0	D	0.747	deleterious	N	0.50515808	None	None	N
F/W	0.8293	likely_pathogenic	0.8156	pathogenic	-0.569	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
F/Y	0.3701	ambiguous	0.3778	ambiguous	-0.762	Destabilizing	0.999	D	0.657	neutral	N	0.473605809	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.