TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26050	78373;78374;78375	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
N2AB	24409	73450;73451;73452	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
N2A	23482	70669;70670;70671	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
N2B	16985	51178;51179;51180	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
Novex-1	17110	51553;51554;51555	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
Novex-2	17177	51754;51755;51756	chr2:178567984;178567983;178567982	chr2:179432711;179432710;179432709
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: Fn3-77
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1568
• 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	0.003	N	0.191	0.284	0.229264304666	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43308E-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	0.7912	likely_pathogenic	0.8144	pathogenic	-2.386	Highly Destabilizing	0.742	D	0.521	neutral	None	None	None	None	N
F/C	0.3219	likely_benign	0.344	ambiguous	-1.537	Destabilizing	0.994	D	0.615	neutral	N	0.467863292	None	None	N
F/D	0.9643	likely_pathogenic	0.9716	pathogenic	-2.283	Highly Destabilizing	0.984	D	0.637	neutral	None	None	None	None	N
F/E	0.9532	likely_pathogenic	0.9614	pathogenic	-2.11	Highly Destabilizing	0.953	D	0.63	neutral	None	None	None	None	N
F/G	0.8872	likely_pathogenic	0.8992	pathogenic	-2.781	Highly Destabilizing	0.854	D	0.62	neutral	None	None	None	None	N
F/H	0.6749	likely_pathogenic	0.7196	pathogenic	-1.081	Destabilizing	0.91	D	0.521	neutral	None	None	None	None	N
F/I	0.401	ambiguous	0.3961	ambiguous	-1.132	Destabilizing	0.521	D	0.423	neutral	N	0.471293106	None	None	N
F/K	0.9448	likely_pathogenic	0.9514	pathogenic	-1.994	Destabilizing	0.953	D	0.629	neutral	None	None	None	None	N
F/L	0.8364	likely_pathogenic	0.8012	pathogenic	-1.132	Destabilizing	0.003	N	0.191	neutral	N	0.495121939	None	None	N
F/M	0.5321	ambiguous	0.5022	ambiguous	-0.816	Destabilizing	0.91	D	0.417	neutral	None	None	None	None	N
F/N	0.8581	likely_pathogenic	0.8843	pathogenic	-2.419	Highly Destabilizing	0.953	D	0.639	neutral	None	None	None	None	N
F/P	0.9982	likely_pathogenic	0.9984	pathogenic	-1.554	Destabilizing	0.984	D	0.667	neutral	None	None	None	None	N
F/Q	0.8687	likely_pathogenic	0.8796	pathogenic	-2.365	Highly Destabilizing	0.984	D	0.667	neutral	None	None	None	None	N
F/R	0.8992	likely_pathogenic	0.9102	pathogenic	-1.465	Destabilizing	0.953	D	0.639	neutral	None	None	None	None	N
F/S	0.7196	likely_pathogenic	0.7806	pathogenic	-3.071	Highly Destabilizing	0.815	D	0.574	neutral	N	0.50598436	None	None	N
F/T	0.8092	likely_pathogenic	0.8349	pathogenic	-2.792	Highly Destabilizing	0.742	D	0.548	neutral	None	None	None	None	N
F/V	0.3848	ambiguous	0.392	ambiguous	-1.554	Destabilizing	0.521	D	0.457	neutral	N	0.518284014	None	None	N
F/W	0.4945	ambiguous	0.524	ambiguous	-0.202	Destabilizing	0.953	D	0.434	neutral	None	None	None	None	N
F/Y	0.1236	likely_benign	0.1431	benign	-0.533	Destabilizing	0.001	N	0.145	neutral	N	0.426414003	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.