TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29094	87505;87506;87507	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
N2AB	27453	82582;82583;82584	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
N2A	26526	79801;79802;79803	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
N2B	20029	60310;60311;60312	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
Novex-1	20154	60685;60686;60687	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
Novex-2	20221	60886;60887;60888	chr2:178558074;178558073;178558072	chr2:179422801;179422800;179422799
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-145
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.6873
• 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	rs199501185	0.852	0.992	N	0.521	0.294	None	gnomAD-2.1.1	1.12659E-04	None	None	None	None	N	None	6.46E-05	5.79E-05	None	0	5.57E-05	None	3.27E-05	None	0	2.04659E-04	0
E/K	rs199501185	0.852	0.992	N	0.521	0.294	None	gnomAD-3.1.2	8.55E-05	None	None	None	None	N	None	1.20715E-04	1.30976E-04	0	0	0	None	0	0	8.82E-05	0	0
E/K	rs199501185	0.852	0.992	N	0.521	0.294	None	gnomAD-4.0.0	1.43146E-04	None	None	None	None	N	None	6.67557E-05	6.66733E-05	None	0	4.45712E-05	None	0	1.6442E-04	1.76294E-04	5.48968E-05	9.60584E-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
E/A	0.2137	likely_benign	0.1828	benign	-0.497	Destabilizing	0.978	D	0.531	neutral	D	0.530229883	None	None	N
E/C	0.8878	likely_pathogenic	0.8378	pathogenic	0.058	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/D	0.1018	likely_benign	0.0957	benign	-0.635	Destabilizing	0.054	N	0.219	neutral	N	0.463159529	None	None	N
E/F	0.8329	likely_pathogenic	0.7675	pathogenic	-0.564	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
E/G	0.2757	likely_benign	0.2321	benign	-0.734	Destabilizing	0.978	D	0.52	neutral	N	0.498507574	None	None	N
E/H	0.5676	likely_pathogenic	0.4529	ambiguous	-0.725	Destabilizing	0.999	D	0.506	neutral	None	None	None	None	N
E/I	0.3921	ambiguous	0.3425	ambiguous	0.101	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/K	0.2805	likely_benign	0.2134	benign	0.071	Stabilizing	0.992	D	0.521	neutral	N	0.491575494	None	None	N
E/L	0.5327	ambiguous	0.457	ambiguous	0.101	Stabilizing	0.998	D	0.625	neutral	None	None	None	None	N
E/M	0.531	ambiguous	0.4641	ambiguous	0.484	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	N
E/N	0.243	likely_benign	0.2121	benign	-0.159	Destabilizing	0.995	D	0.481	neutral	None	None	None	None	N
E/P	0.9713	likely_pathogenic	0.9463	pathogenic	-0.077	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
E/Q	0.2019	likely_benign	0.1666	benign	-0.132	Destabilizing	0.909	D	0.285	neutral	D	0.522591834	None	None	N
E/R	0.4745	ambiguous	0.3714	ambiguous	0.129	Stabilizing	0.995	D	0.496	neutral	None	None	None	None	N
E/S	0.2439	likely_benign	0.2052	benign	-0.357	Destabilizing	0.983	D	0.493	neutral	None	None	None	None	N
E/T	0.2471	likely_benign	0.2063	benign	-0.172	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
E/V	0.2372	likely_benign	0.2046	benign	-0.077	Destabilizing	0.997	D	0.587	neutral	N	0.517012656	None	None	N
E/W	0.952	likely_pathogenic	0.9227	pathogenic	-0.478	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
E/Y	0.7288	likely_pathogenic	0.6395	pathogenic	-0.34	Destabilizing	0.999	D	0.637	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.