TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7282	22069;22070;22071	chr2:178723163;178723162;178723161	chr2:179587890;179587889;179587888
N2AB	6965	21118;21119;21120	chr2:178723163;178723162;178723161	chr2:179587890;179587889;179587888
N2A	6038	18337;18338;18339	chr2:178723163;178723162;178723161	chr2:179587890;179587889;179587888
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-57
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.8284
• 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
E/D	None	None	0.026	N	0.231	0.105	0.0716867268079	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs757098573	0.038	0.026	N	0.306	0.196	0.180583059064	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/K	rs778532757	0.694	0.896	N	0.419	0.239	0.226586394389	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4E-05	1.57E-05	0
E/K	rs778532757	0.694	0.896	N	0.419	0.239	0.226586394389	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	7.35E-05	0	0
E/K	rs778532757	0.694	0.896	N	0.419	0.239	0.226586394389	gnomAD-4.0.0	2.97507E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.12539E-05	0	3.89947E-05	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
E/A	0.1883	likely_benign	0.2403	benign	-0.155	Destabilizing	0.103	N	0.279	neutral	N	0.459388644	None	None	I
E/C	0.929	likely_pathogenic	0.9521	pathogenic	-0.358	Destabilizing	0.999	D	0.533	neutral	None	None	None	None	I
E/D	0.1101	likely_benign	0.1593	benign	-0.418	Destabilizing	0.026	N	0.231	neutral	N	0.445663406	None	None	I
E/F	0.8792	likely_pathogenic	0.9247	pathogenic	0.008	Stabilizing	0.996	D	0.493	neutral	None	None	None	None	I
E/G	0.1229	likely_benign	0.1532	benign	-0.32	Destabilizing	0.026	N	0.306	neutral	N	0.414876353	None	None	I
E/H	0.5714	likely_pathogenic	0.6686	pathogenic	0.619	Stabilizing	0.999	D	0.388	neutral	None	None	None	None	I
E/I	0.6284	likely_pathogenic	0.734	pathogenic	0.237	Stabilizing	0.988	D	0.495	neutral	None	None	None	None	I
E/K	0.1502	likely_benign	0.1805	benign	0.319	Stabilizing	0.896	D	0.419	neutral	N	0.453539294	None	None	I
E/L	0.5932	likely_pathogenic	0.697	pathogenic	0.237	Stabilizing	0.976	D	0.461	neutral	None	None	None	None	I
E/M	0.6563	likely_pathogenic	0.7382	pathogenic	-0.02	Destabilizing	0.999	D	0.485	neutral	None	None	None	None	I
E/N	0.263	likely_benign	0.3646	ambiguous	-0.146	Destabilizing	0.952	D	0.376	neutral	None	None	None	None	I
E/P	0.377	ambiguous	0.4817	ambiguous	0.125	Stabilizing	0.988	D	0.411	neutral	None	None	None	None	I
E/Q	0.1743	likely_benign	0.2033	benign	-0.091	Destabilizing	0.984	D	0.369	neutral	N	0.465656068	None	None	I
E/R	0.2642	likely_benign	0.3069	benign	0.671	Stabilizing	0.988	D	0.384	neutral	None	None	None	None	I
E/S	0.2094	likely_benign	0.2706	benign	-0.255	Destabilizing	0.851	D	0.391	neutral	None	None	None	None	I
E/T	0.3313	likely_benign	0.4213	ambiguous	-0.106	Destabilizing	0.919	D	0.426	neutral	None	None	None	None	I
E/V	0.4034	ambiguous	0.4969	ambiguous	0.125	Stabilizing	0.968	D	0.407	neutral	N	0.475886737	None	None	I
E/W	0.9235	likely_pathogenic	0.9513	pathogenic	0.128	Stabilizing	0.999	D	0.581	neutral	None	None	None	None	I
E/Y	0.7585	likely_pathogenic	0.8391	pathogenic	0.245	Stabilizing	0.996	D	0.461	neutral	None	None	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.