TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7704	23335;23336;23337	chr2:178720652;178720651;178720650	chr2:179585379;179585378;179585377
N2AB	7387	22384;22385;22386	chr2:178720652;178720651;178720650	chr2:179585379;179585378;179585377
N2A	6460	19603;19604;19605	chr2:178720652;178720651;178720650	chr2:179585379;179585378;179585377
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-62
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1775
• 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	rs2078208221	None	0.06	N	0.335	0.476	0.390531646278	gnomAD-4.0.0	1.6605E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.55284E-05	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	0.9959	likely_pathogenic	0.9929	pathogenic	-3.021	Highly Destabilizing	0.997	D	0.79	deleterious	None	None	None	None	N
F/C	0.9834	likely_pathogenic	0.9657	pathogenic	-1.993	Destabilizing	1.0	D	0.859	deleterious	D	0.571189126	None	None	N
F/D	0.9994	likely_pathogenic	0.9991	pathogenic	-3.099	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
F/E	0.9993	likely_pathogenic	0.9989	pathogenic	-3.003	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
F/G	0.9984	likely_pathogenic	0.9975	pathogenic	-3.365	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
F/H	0.995	likely_pathogenic	0.9926	pathogenic	-1.62	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
F/I	0.8357	likely_pathogenic	0.7229	pathogenic	-1.927	Destabilizing	0.96	D	0.683	prob.neutral	N	0.491799304	None	None	N
F/K	0.9992	likely_pathogenic	0.9988	pathogenic	-1.784	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
F/L	0.9896	likely_pathogenic	0.981	pathogenic	-1.927	Destabilizing	0.06	N	0.335	neutral	N	0.504351059	None	None	N
F/M	0.9568	likely_pathogenic	0.929	pathogenic	-1.726	Destabilizing	0.954	D	0.717	prob.delet.	None	None	None	None	N
F/N	0.9975	likely_pathogenic	0.9962	pathogenic	-1.936	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9992	pathogenic	-2.295	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
F/Q	0.9987	likely_pathogenic	0.998	pathogenic	-2.141	Highly Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
F/R	0.9978	likely_pathogenic	0.9967	pathogenic	-0.964	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	N
F/S	0.9964	likely_pathogenic	0.9939	pathogenic	-2.61	Highly Destabilizing	1.0	D	0.844	deleterious	D	0.570682147	None	None	N
F/T	0.9967	likely_pathogenic	0.9941	pathogenic	-2.419	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
F/V	0.8976	likely_pathogenic	0.8218	pathogenic	-2.295	Highly Destabilizing	0.946	D	0.717	prob.delet.	N	0.518238579	None	None	N
F/W	0.9604	likely_pathogenic	0.9451	pathogenic	-0.776	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
F/Y	0.8262	likely_pathogenic	0.7921	pathogenic	-1.088	Destabilizing	0.993	D	0.677	prob.neutral	D	0.534727127	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.