TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6070	18433;18434;18435	chr2:178730192;178730191;178730190	chr2:179594919;179594918;179594917
N2AB	5753	17482;17483;17484	chr2:178730192;178730191;178730190	chr2:179594919;179594918;179594917
N2A	4826	14701;14702;14703	chr2:178730192;178730191;178730190	chr2:179594919;179594918;179594917
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-44
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1429
• 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
E/Q	rs1238374094	-0.931	1.0	N	0.577	0.293	0.327952845175	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
E/Q	rs1238374094	-0.931	1.0	N	0.577	0.293	0.327952845175	gnomAD-4.0.0	1.59202E-06	None	None	None	None	N	None	0	0	None	0	2.77886E-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	0.3829	ambiguous	0.414	ambiguous	-1.256	Destabilizing	0.767	D	0.376	neutral	N	0.488997693	None	None	N
E/C	0.9479	likely_pathogenic	0.9508	pathogenic	-0.717	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.4423	ambiguous	0.4709	ambiguous	-1.484	Destabilizing	0.998	D	0.417	neutral	N	0.486644289	None	None	N
E/F	0.8609	likely_pathogenic	0.8735	pathogenic	-0.789	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/G	0.6121	likely_pathogenic	0.6692	pathogenic	-1.669	Destabilizing	0.996	D	0.572	neutral	N	0.50178603	None	None	N
E/H	0.7257	likely_pathogenic	0.7405	pathogenic	-0.946	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	N
E/I	0.5206	ambiguous	0.5364	ambiguous	-0.095	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/K	0.5343	ambiguous	0.5884	pathogenic	-0.983	Destabilizing	0.998	D	0.427	neutral	N	0.508411816	None	None	N
E/L	0.6206	likely_pathogenic	0.6356	pathogenic	-0.095	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/M	0.6672	likely_pathogenic	0.6861	pathogenic	0.527	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/N	0.6926	likely_pathogenic	0.7271	pathogenic	-1.397	Destabilizing	1.0	D	0.62	neutral	None	None	None	None	N
E/P	0.991	likely_pathogenic	0.9932	pathogenic	-0.464	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/Q	0.2557	likely_benign	0.2649	benign	-1.212	Destabilizing	1.0	D	0.577	neutral	N	0.507315738	None	None	N
E/R	0.6399	likely_pathogenic	0.6707	pathogenic	-0.789	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/S	0.5089	ambiguous	0.5433	ambiguous	-1.944	Destabilizing	0.994	D	0.419	neutral	None	None	None	None	N
E/T	0.474	ambiguous	0.5168	ambiguous	-1.566	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/V	0.3261	likely_benign	0.341	ambiguous	-0.464	Destabilizing	0.999	D	0.662	neutral	N	0.504294075	None	None	N
E/W	0.954	likely_pathogenic	0.9589	pathogenic	-0.616	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/Y	0.798	likely_pathogenic	0.8094	pathogenic	-0.507	Destabilizing	1.0	D	0.752	deleterious	None	None	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.