TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19191	57796;57797;57798	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
N2AB	17550	52873;52874;52875	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
N2A	16623	50092;50093;50094	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
N2B	10126	30601;30602;30603	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
Novex-1	10251	30976;30977;30978	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
Novex-2	10318	31177;31178;31179	chr2:178595783;178595782;178595781	chr2:179460510;179460509;179460508
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: Fn3-27
• Domain position: 9
• Structural Position: 10
• Q(SASA): 0.0909
• 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/L	None	None	0.046	N	0.384	0.225	0.255777322467	gnomAD-4.0.0	6.87617E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02144E-07	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	0.9586	likely_pathogenic	0.974	pathogenic	-2.497	Highly Destabilizing	0.953	D	0.734	prob.delet.	None	None	None	None	N
F/C	0.7892	likely_pathogenic	0.8613	pathogenic	-1.431	Destabilizing	0.999	D	0.79	deleterious	N	0.498698175	None	None	N
F/D	0.9925	likely_pathogenic	0.9959	pathogenic	-3.258	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
F/E	0.9926	likely_pathogenic	0.9953	pathogenic	-3.03	Highly Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
F/G	0.9846	likely_pathogenic	0.991	pathogenic	-2.954	Highly Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
F/H	0.9683	likely_pathogenic	0.9817	pathogenic	-1.76	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
F/I	0.3554	ambiguous	0.3946	ambiguous	-1.004	Destabilizing	0.885	D	0.687	prob.neutral	N	0.413444705	None	None	N
F/K	0.9927	likely_pathogenic	0.9953	pathogenic	-1.85	Destabilizing	0.993	D	0.816	deleterious	None	None	None	None	N
F/L	0.8714	likely_pathogenic	0.893	pathogenic	-1.004	Destabilizing	0.046	N	0.384	neutral	N	0.405017223	None	None	N
F/M	0.7607	likely_pathogenic	0.7818	pathogenic	-0.781	Destabilizing	0.986	D	0.735	prob.delet.	None	None	None	None	N
F/N	0.9798	likely_pathogenic	0.9867	pathogenic	-2.433	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
F/P	0.9889	likely_pathogenic	0.9936	pathogenic	-1.514	Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
F/Q	0.9872	likely_pathogenic	0.9915	pathogenic	-2.308	Highly Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
F/R	0.9833	likely_pathogenic	0.9898	pathogenic	-1.586	Destabilizing	0.993	D	0.848	deleterious	None	None	None	None	N
F/S	0.9588	likely_pathogenic	0.9776	pathogenic	-2.951	Highly Destabilizing	0.991	D	0.751	deleterious	N	0.504679998	None	None	N
F/T	0.9609	likely_pathogenic	0.9754	pathogenic	-2.605	Highly Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
F/V	0.4544	ambiguous	0.5155	ambiguous	-1.514	Destabilizing	0.885	D	0.677	prob.neutral	N	0.429528879	None	None	N
F/W	0.8072	likely_pathogenic	0.8592	pathogenic	-0.109	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
F/Y	0.5121	ambiguous	0.5973	pathogenic	-0.485	Destabilizing	0.969	D	0.581	neutral	N	0.505720148	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.