TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23285	70078;70079;70080	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
N2AB	21644	65155;65156;65157	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
N2A	20717	62374;62375;62376	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
N2B	14220	42883;42884;42885	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
Novex-1	14345	43258;43259;43260	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
Novex-2	14412	43459;43460;43461	chr2:178576279;178576278;178576277	chr2:179441006;179441005;179441004
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: Fn3-57
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.0094
• 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/G	None	None	0.22	N	0.502	0.226	0.245660935333	gnomAD-4.0.0	7.56972E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.022E-06	0	1.66739E-05
E/K	rs376870149	0.66	0.613	N	0.549	0.228	None	gnomAD-2.1.1	5.93E-05	None	None	None	None	N	None	3.35008E-04	8.81E-05	None	0	0	None	3.51E-05	None	0	3.24E-05	0
E/K	rs376870149	0.66	0.613	N	0.549	0.228	None	gnomAD-3.1.2	1.97345E-04	None	None	None	None	N	None	6.27837E-04	6.56E-05	0	0	0	None	0	0	2.94E-05	2.07211E-04	0
E/K	rs376870149	0.66	0.613	N	0.549	0.228	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs376870149	0.66	0.613	N	0.549	0.228	None	gnomAD-4.0.0	6.41997E-05	None	None	None	None	N	None	4.83637E-04	8.53009E-05	None	0	2.24014E-05	None	0	0	4.93186E-05	2.2412E-05	1.61233E-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	0.101	likely_benign	0.1046	benign	0.03	Stabilizing	0.22	N	0.556	neutral	N	0.496010161	None	None	N
E/C	0.6901	likely_pathogenic	0.697	pathogenic	-0.225	Destabilizing	0.968	D	0.632	neutral	None	None	None	None	N
E/D	0.0777	likely_benign	0.0775	benign	-0.319	Destabilizing	None	N	0.278	neutral	N	0.43215347	None	None	N
E/F	0.5996	likely_pathogenic	0.6095	pathogenic	-0.127	Destabilizing	0.89	D	0.596	neutral	None	None	None	None	N
E/G	0.104	likely_benign	0.1061	benign	-0.045	Destabilizing	0.22	N	0.502	neutral	N	0.463164237	None	None	N
E/H	0.3192	likely_benign	0.3156	benign	0.522	Stabilizing	0.726	D	0.621	neutral	None	None	None	None	N
E/I	0.2443	likely_benign	0.2462	benign	0.164	Stabilizing	0.726	D	0.595	neutral	None	None	None	None	N
E/K	0.092	likely_benign	0.088	benign	0.311	Stabilizing	0.613	D	0.549	neutral	N	0.493239215	None	None	N
E/L	0.2551	likely_benign	0.2612	benign	0.164	Stabilizing	0.567	D	0.58	neutral	None	None	None	None	N
E/M	0.3013	likely_benign	0.3037	benign	-0.076	Destabilizing	0.968	D	0.591	neutral	None	None	None	None	N
E/N	0.1493	likely_benign	0.1479	benign	0.256	Stabilizing	0.157	N	0.563	neutral	None	None	None	None	N
E/P	0.2833	likely_benign	0.2921	benign	0.135	Stabilizing	0.726	D	0.579	neutral	None	None	None	None	N
E/Q	0.1289	likely_benign	0.1265	benign	0.226	Stabilizing	0.417	N	0.527	neutral	N	0.492719139	None	None	N
E/R	0.1865	likely_benign	0.1795	benign	0.513	Stabilizing	0.567	D	0.599	neutral	None	None	None	None	N
E/S	0.1267	likely_benign	0.1295	benign	0.069	Stabilizing	0.157	N	0.559	neutral	None	None	None	None	N
E/T	0.1235	likely_benign	0.1264	benign	0.135	Stabilizing	0.272	N	0.528	neutral	None	None	None	None	N
E/V	0.1468	likely_benign	0.1501	benign	0.135	Stabilizing	0.667	D	0.533	neutral	N	0.482984935	None	None	N
E/W	0.804	likely_pathogenic	0.8019	pathogenic	-0.13	Destabilizing	0.968	D	0.643	neutral	None	None	None	None	N
E/Y	0.4687	ambiguous	0.4723	ambiguous	0.083	Stabilizing	0.89	D	0.587	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.