TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29772	89539;89540;89541	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
N2AB	28131	84616;84617;84618	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
N2A	27204	81835;81836;81837	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
N2B	20707	62344;62345;62346	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
Novex-1	20832	62719;62720;62721	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
Novex-2	20899	62920;62921;62922	chr2:178553691;178553690;178553689	chr2:179418418;179418417;179418416
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: Fn3-105
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1846
• 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/K	None	-1.494	0.271	N	0.649	0.265	None	gnomAD-2.1.1	2.394E-04	None	None	None	None	N	None	4.13223E-04	2.82933E-04	None	9.68E-05	0	None	3.27E-05	None	0	3.36432E-04	2.81294E-04
E/K	None	-1.494	0.271	N	0.649	0.265	None	gnomAD-3.1.2	2.82631E-04	None	None	None	None	N	None	4.58494E-04	1.31113E-04	0	0	0	None	0	0	3.08715E-04	2.06954E-04	0
E/K	None	-1.494	0.271	N	0.649	0.265	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	None	-1.494	0.271	N	0.649	0.265	None	gnomAD-4.0.0	2.80701E-04	None	None	None	None	N	None	4.26451E-04	2.66684E-04	None	3.37792E-05	0	None	0	1.65017E-04	3.29715E-04	3.29366E-05	1.76068E-04
E/Q	rs200503016	None	0.01	N	0.439	0.148	0.178374595973	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs200503016	None	0.01	N	0.439	0.148	0.178374595973	gnomAD-4.0.0	6.57281E-06	None	None	None	None	N	None	2.41313E-05	0	None	0	0	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	0.2329	likely_benign	0.2393	benign	-2.525	Highly Destabilizing	None	N	0.453	neutral	N	0.51527675	None	None	N
E/C	0.8673	likely_pathogenic	0.8795	pathogenic	-1.338	Destabilizing	0.824	D	0.704	prob.neutral	None	None	None	None	N
E/D	0.3484	ambiguous	0.3214	benign	-1.798	Destabilizing	None	N	0.464	neutral	N	0.492065779	None	None	N
E/F	0.8969	likely_pathogenic	0.895	pathogenic	-2.282	Highly Destabilizing	0.555	D	0.693	prob.neutral	None	None	None	None	N
E/G	0.3455	ambiguous	0.3679	ambiguous	-2.869	Highly Destabilizing	None	N	0.513	neutral	N	0.517051177	None	None	N
E/H	0.6577	likely_pathogenic	0.6573	pathogenic	-1.879	Destabilizing	0.38	N	0.631	neutral	None	None	None	None	N
E/I	0.7736	likely_pathogenic	0.7621	pathogenic	-1.516	Destabilizing	0.38	N	0.693	prob.neutral	None	None	None	None	N
E/K	0.4954	ambiguous	0.4853	ambiguous	-1.989	Destabilizing	0.271	N	0.649	neutral	N	0.491132108	None	None	N
E/L	0.7675	likely_pathogenic	0.7581	pathogenic	-1.516	Destabilizing	0.235	N	0.674	neutral	None	None	None	None	N
E/M	0.6376	likely_pathogenic	0.6476	pathogenic	-0.683	Destabilizing	0.824	D	0.677	prob.neutral	None	None	None	None	N
E/N	0.5648	likely_pathogenic	0.5464	ambiguous	-2.025	Highly Destabilizing	0.149	N	0.626	neutral	None	None	None	None	N
E/P	0.9976	likely_pathogenic	0.9964	pathogenic	-1.844	Destabilizing	0.38	N	0.635	neutral	None	None	None	None	N
E/Q	0.1539	likely_benign	0.1499	benign	-1.832	Destabilizing	0.01	N	0.439	neutral	N	0.476672252	None	None	N
E/R	0.6186	likely_pathogenic	0.6102	pathogenic	-1.658	Destabilizing	0.235	N	0.642	neutral	None	None	None	None	N
E/S	0.2845	likely_benign	0.2966	benign	-2.797	Highly Destabilizing	0.081	N	0.611	neutral	None	None	None	None	N
E/T	0.4919	ambiguous	0.4984	ambiguous	-2.455	Highly Destabilizing	0.081	N	0.597	neutral	None	None	None	None	N
E/V	0.5739	likely_pathogenic	0.5605	ambiguous	-1.844	Destabilizing	0.062	N	0.66	neutral	N	0.504680913	None	None	N
E/W	0.9653	likely_pathogenic	0.9597	pathogenic	-2.194	Highly Destabilizing	0.935	D	0.709	prob.delet.	None	None	None	None	N
E/Y	0.8704	likely_pathogenic	0.8575	pathogenic	-2.049	Highly Destabilizing	0.555	D	0.669	neutral	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.