TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9291	28096;28097;28098	chr2:178711959;178711958;178711957	chr2:179576686;179576685;179576684
N2AB	8974	27145;27146;27147	chr2:178711959;178711958;178711957	chr2:179576686;179576685;179576684
N2A	8047	24364;24365;24366	chr2:178711959;178711958;178711957	chr2:179576686;179576685;179576684
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-78
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.588
• Predicted PPI site: I

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	rs754982924	-0.986	0.003	N	0.204	0.222	0.607559715422	gnomAD-2.1.1	1.25E-05	None	None	None	None	I	None	0	2.99E-05	None	0	0	None	0	None	0	1.84E-05	0
F/S	rs754982924	-0.986	0.003	N	0.204	0.222	0.607559715422	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
F/S	rs754982924	-0.986	0.003	N	0.204	0.222	0.607559715422	gnomAD-4.0.0	1.04382E-05	None	None	None	None	I	None	0	1.72849E-05	None	0	0	None	0	0	1.21922E-05	0	5.78737E-05

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	0.1842	likely_benign	0.2084	benign	-1.425	Destabilizing	0.061	N	0.269	neutral	None	None	None	None	I
F/C	0.1509	likely_benign	0.2383	benign	-0.49	Destabilizing	0.921	D	0.531	neutral	N	0.47195237	None	None	I
F/D	0.3581	ambiguous	0.3963	ambiguous	0.668	Stabilizing	0.418	N	0.534	neutral	None	None	None	None	I
F/E	0.4222	ambiguous	0.4366	ambiguous	0.685	Stabilizing	0.228	N	0.453	neutral	None	None	None	None	I
F/G	0.4252	ambiguous	0.4967	ambiguous	-1.676	Destabilizing	0.129	N	0.424	neutral	None	None	None	None	I
F/H	0.245	likely_benign	0.2582	benign	-0.083	Destabilizing	0.001	N	0.156	neutral	None	None	None	None	I
F/I	0.0687	likely_benign	0.0801	benign	-0.739	Destabilizing	0.101	N	0.404	neutral	N	0.413346784	None	None	I
F/K	0.383	ambiguous	0.3577	ambiguous	-0.303	Destabilizing	0.129	N	0.421	neutral	None	None	None	None	I
F/L	0.4022	ambiguous	0.4042	ambiguous	-0.739	Destabilizing	None	N	0.12	neutral	N	0.420446115	None	None	I
F/M	0.2158	likely_benign	0.2181	benign	-0.511	Destabilizing	0.716	D	0.447	neutral	None	None	None	None	I
F/N	0.2193	likely_benign	0.2198	benign	-0.185	Destabilizing	0.228	N	0.482	neutral	None	None	None	None	I
F/P	0.7089	likely_pathogenic	0.7873	pathogenic	-0.951	Destabilizing	0.593	D	0.595	neutral	None	None	None	None	I
F/Q	0.3455	ambiguous	0.352	ambiguous	-0.27	Destabilizing	0.418	N	0.579	neutral	None	None	None	None	I
F/R	0.2905	likely_benign	0.2917	benign	0.249	Stabilizing	0.001	N	0.289	neutral	None	None	None	None	I
F/S	0.1145	likely_benign	0.1304	benign	-1.023	Destabilizing	0.003	N	0.204	neutral	N	0.389736419	None	None	I
F/T	0.1443	likely_benign	0.1455	benign	-0.917	Destabilizing	0.129	N	0.421	neutral	None	None	None	None	I
F/V	0.0685	likely_benign	0.0797	benign	-0.951	Destabilizing	0.101	N	0.377	neutral	N	0.370345368	None	None	I
F/W	0.3236	likely_benign	0.4094	ambiguous	-0.23	Destabilizing	0.94	D	0.483	neutral	None	None	None	None	I
F/Y	0.0921	likely_benign	0.1085	benign	-0.298	Destabilizing	0.183	N	0.436	neutral	N	0.431471185	None	None	I

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.