TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26148	78667;78668;78669	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
N2AB	24507	73744;73745;73746	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
N2A	23580	70963;70964;70965	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
N2B	17083	51472;51473;51474	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
Novex-1	17208	51847;51848;51849	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
Novex-2	17275	52048;52049;52050	chr2:178567690;178567689;178567688	chr2:179432417;179432416;179432415
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: Fn3-78
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.2324
• 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	rs956398655	None	0.999	N	0.747	0.466	0.685023438539	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/C	rs956398655	None	0.999	N	0.747	0.466	0.685023438539	gnomAD-4.0.0	5.13554E-06	None	None	None	None	N	None	1.69285E-05	0	None	0	0	None	0	2.24417E-04	4.79922E-06	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	0.9896	likely_pathogenic	0.9895	pathogenic	-2.179	Highly Destabilizing	0.916	D	0.581	neutral	None	None	None	None	N
F/C	0.9044	likely_pathogenic	0.8915	pathogenic	-1.385	Destabilizing	0.999	D	0.747	deleterious	N	0.504744287	None	None	N
F/D	0.9974	likely_pathogenic	0.997	pathogenic	-1.264	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
F/E	0.9969	likely_pathogenic	0.9967	pathogenic	-1.112	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
F/G	0.9938	likely_pathogenic	0.9932	pathogenic	-2.571	Highly Destabilizing	0.987	D	0.711	prob.delet.	None	None	None	None	N
F/H	0.9499	likely_pathogenic	0.9478	pathogenic	-0.817	Destabilizing	0.975	D	0.749	deleterious	None	None	None	None	N
F/I	0.938	likely_pathogenic	0.9367	pathogenic	-0.966	Destabilizing	0.967	D	0.575	neutral	N	0.477053551	None	None	N
F/K	0.9962	likely_pathogenic	0.9962	pathogenic	-1.517	Destabilizing	0.987	D	0.763	deleterious	None	None	None	None	N
F/L	0.9925	likely_pathogenic	0.9921	pathogenic	-0.966	Destabilizing	0.805	D	0.455	neutral	N	0.508051164	None	None	N
F/M	0.9453	likely_pathogenic	0.9415	pathogenic	-0.767	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
F/N	0.9876	likely_pathogenic	0.9858	pathogenic	-1.793	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-1.369	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
F/Q	0.9918	likely_pathogenic	0.9916	pathogenic	-1.745	Destabilizing	0.987	D	0.785	deleterious	None	None	None	None	N
F/R	0.9906	likely_pathogenic	0.9905	pathogenic	-0.995	Destabilizing	0.987	D	0.786	deleterious	None	None	None	None	N
F/S	0.986	likely_pathogenic	0.9844	pathogenic	-2.589	Highly Destabilizing	0.983	D	0.704	prob.neutral	N	0.499730163	None	None	N
F/T	0.9916	likely_pathogenic	0.9909	pathogenic	-2.332	Highly Destabilizing	0.987	D	0.713	prob.delet.	None	None	None	None	N
F/V	0.9188	likely_pathogenic	0.9152	pathogenic	-1.369	Destabilizing	0.892	D	0.564	neutral	N	0.465551752	None	None	N
F/W	0.8696	likely_pathogenic	0.8602	pathogenic	0.007	Stabilizing	0.997	D	0.61	neutral	None	None	None	None	N
F/Y	0.2585	likely_benign	0.244	benign	-0.305	Destabilizing	0.025	N	0.325	neutral	N	0.447154634	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.