TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7917	23974;23975;23976	chr2:178719743;178719742;178719741	chr2:179584470;179584469;179584468
N2AB	7600	23023;23024;23025	chr2:178719743;178719742;178719741	chr2:179584470;179584469;179584468
N2A	6673	20242;20243;20244	chr2:178719743;178719742;178719741	chr2:179584470;179584469;179584468
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-64
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7516
• 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/K	rs1288323003	0.801	0.37	N	0.373	0.28	0.318252033908	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/K	rs1288323003	0.801	0.37	N	0.373	0.28	0.318252033908	gnomAD-4.0.0	2.05276E-06	None	None	None	None	I	None	0	0	None	0	7.5582E-05	None	0	0	0	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	0.1566	likely_benign	0.1714	benign	-0.044	Destabilizing	0.37	N	0.42	neutral	N	0.484264432	None	None	I
E/C	0.8967	likely_pathogenic	0.9028	pathogenic	-0.111	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
E/D	0.1531	likely_benign	0.161	benign	-0.257	Destabilizing	0.989	D	0.482	neutral	N	0.49830331	None	None	I
E/F	0.772	likely_pathogenic	0.7805	pathogenic	-0.024	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
E/G	0.2448	likely_benign	0.2551	benign	-0.179	Destabilizing	0.978	D	0.612	neutral	D	0.523234874	None	None	I
E/H	0.4978	ambiguous	0.5259	ambiguous	0.511	Stabilizing	1.0	D	0.483	neutral	None	None	None	None	I
E/I	0.3815	ambiguous	0.3942	ambiguous	0.256	Stabilizing	0.998	D	0.667	neutral	None	None	None	None	I
E/K	0.1692	likely_benign	0.1815	benign	0.502	Stabilizing	0.37	N	0.373	neutral	N	0.503736715	None	None	I
E/L	0.411	ambiguous	0.4298	ambiguous	0.256	Stabilizing	0.995	D	0.604	neutral	None	None	None	None	I
E/M	0.4949	ambiguous	0.5172	ambiguous	0.077	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	I
E/N	0.3082	likely_benign	0.3255	benign	0.206	Stabilizing	0.998	D	0.503	neutral	None	None	None	None	I
E/P	0.3637	ambiguous	0.3925	ambiguous	0.175	Stabilizing	0.998	D	0.56	neutral	None	None	None	None	I
E/Q	0.1482	likely_benign	0.1584	benign	0.228	Stabilizing	0.994	D	0.467	neutral	D	0.527536294	None	None	I
E/R	0.2838	likely_benign	0.3028	benign	0.72	Stabilizing	0.99	D	0.495	neutral	None	None	None	None	I
E/S	0.2308	likely_benign	0.2396	benign	0.072	Stabilizing	0.967	D	0.517	neutral	None	None	None	None	I
E/T	0.2737	likely_benign	0.2903	benign	0.192	Stabilizing	0.983	D	0.551	neutral	None	None	None	None	I
E/V	0.2206	likely_benign	0.2325	benign	0.175	Stabilizing	0.994	D	0.561	neutral	N	0.492520093	None	None	I
E/W	0.9227	likely_pathogenic	0.9285	pathogenic	0.051	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/Y	0.6409	likely_pathogenic	0.6589	pathogenic	0.212	Stabilizing	0.999	D	0.641	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.