TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6100	18523;18524;18525	chr2:178730102;178730101;178730100	chr2:179594829;179594828;179594827
N2AB	5783	17572;17573;17574	chr2:178730102;178730101;178730100	chr2:179594829;179594828;179594827
N2A	4856	14791;14792;14793	chr2:178730102;178730101;178730100	chr2:179594829;179594828;179594827
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-44
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3901
• 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	rs761215282	-0.883	0.889	N	0.453	0.333	0.74728673918	gnomAD-2.1.1	8.12E-06	None	None	None	None	N	None	6.49E-05	0	None	0	0	None	3.29E-05	None	0	0	0
F/S	rs761215282	-0.883	0.889	N	0.453	0.333	0.74728673918	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	9.41E-05	0	0	0	0
F/S	rs761215282	-0.883	0.889	N	0.453	0.333	0.74728673918	gnomAD-4.0.0	6.20729E-06	None	None	None	None	N	None	2.67816E-05	0	None	0	0	None	3.1295E-05	0	0	6.60517E-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	0.2896	likely_benign	0.3132	benign	-1.623	Destabilizing	0.983	D	0.586	neutral	None	None	None	None	N
F/C	0.321	likely_benign	0.3557	ambiguous	-0.771	Destabilizing	1.0	D	0.709	prob.delet.	N	0.495581058	None	None	N
F/D	0.5268	ambiguous	0.5744	pathogenic	0.524	Stabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
F/E	0.5817	likely_pathogenic	0.6119	pathogenic	0.559	Stabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
F/G	0.6245	likely_pathogenic	0.6721	pathogenic	-1.891	Destabilizing	0.992	D	0.657	neutral	None	None	None	None	N
F/H	0.3058	likely_benign	0.3225	benign	-0.135	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
F/I	0.1496	likely_benign	0.1686	benign	-0.874	Destabilizing	0.998	D	0.567	neutral	N	0.491210135	None	None	N
F/K	0.5933	likely_pathogenic	0.6129	pathogenic	-0.565	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
F/L	0.6496	likely_pathogenic	0.6817	pathogenic	-0.874	Destabilizing	0.994	D	0.536	neutral	N	0.46148466	None	None	N
F/M	0.4268	ambiguous	0.4434	ambiguous	-0.676	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	N
F/N	0.3572	ambiguous	0.3715	ambiguous	-0.51	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
F/P	0.9598	likely_pathogenic	0.9744	pathogenic	-1.109	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
F/Q	0.4986	ambiguous	0.5204	ambiguous	-0.577	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
F/R	0.4088	ambiguous	0.432	ambiguous	0.043	Stabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
F/S	0.1654	likely_benign	0.1893	benign	-1.387	Destabilizing	0.889	D	0.453	neutral	N	0.492767573	None	None	N
F/T	0.2139	likely_benign	0.2244	benign	-1.262	Destabilizing	0.983	D	0.621	neutral	None	None	None	None	N
F/V	0.157	likely_benign	0.1694	benign	-1.109	Destabilizing	0.994	D	0.631	neutral	N	0.493807723	None	None	N
F/W	0.3846	ambiguous	0.4318	ambiguous	-0.18	Destabilizing	1.0	D	0.569	neutral	None	None	None	None	N
F/Y	0.125	likely_benign	0.1286	benign	-0.327	Destabilizing	0.998	D	0.56	neutral	N	0.511740122	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.