TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5824	17695;17696;17697	chr2:178731195;178731194;178731193	chr2:179595922;179595921;179595920
N2AB	5507	16744;16745;16746	chr2:178731195;178731194;178731193	chr2:179595922;179595921;179595920
N2A	4580	13963;13964;13965	chr2:178731195;178731194;178731193	chr2:179595922;179595921;179595920
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-42
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4126
• 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
T/A	rs750512727	-0.461	0.334	N	0.404	0.119	0.0954503805726	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/A	rs750512727	-0.461	0.334	N	0.404	0.119	0.0954503805726	gnomAD-4.0.0	2.0537E-06	None	None	None	None	N	None	0	2.23914E-05	None	0	0	None	0	0	1.79972E-06	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
T/A	0.0708	likely_benign	0.0675	benign	-0.758	Destabilizing	0.334	N	0.404	neutral	N	0.453186811	None	None	N
T/C	0.3789	ambiguous	0.3801	ambiguous	-0.422	Destabilizing	0.992	D	0.458	neutral	None	None	None	None	N
T/D	0.3328	likely_benign	0.3345	benign	0.323	Stabilizing	0.447	N	0.425	neutral	None	None	None	None	N
T/E	0.2211	likely_benign	0.2278	benign	0.269	Stabilizing	0.021	N	0.271	neutral	None	None	None	None	N
T/F	0.1791	likely_benign	0.1722	benign	-1.209	Destabilizing	0.972	D	0.477	neutral	None	None	None	None	N
T/G	0.2538	likely_benign	0.2372	benign	-0.906	Destabilizing	0.617	D	0.429	neutral	None	None	None	None	N
T/H	0.1933	likely_benign	0.1969	benign	-1.314	Destabilizing	0.92	D	0.464	neutral	None	None	None	None	N
T/I	0.1115	likely_benign	0.1162	benign	-0.474	Destabilizing	0.896	D	0.472	neutral	N	0.491147767	None	None	N
T/K	0.1344	likely_benign	0.1367	benign	-0.328	Destabilizing	0.007	N	0.238	neutral	N	0.428675156	None	None	N
T/L	0.0915	likely_benign	0.0907	benign	-0.474	Destabilizing	0.617	D	0.412	neutral	None	None	None	None	N
T/M	0.081	likely_benign	0.0814	benign	-0.117	Destabilizing	0.972	D	0.454	neutral	None	None	None	None	N
T/N	0.1156	likely_benign	0.114	benign	-0.141	Destabilizing	0.021	N	0.225	neutral	None	None	None	None	N
T/P	0.6124	likely_pathogenic	0.5794	pathogenic	-0.541	Destabilizing	0.963	D	0.461	neutral	N	0.480277412	None	None	N
T/Q	0.166	likely_benign	0.1673	benign	-0.41	Destabilizing	0.617	D	0.431	neutral	None	None	None	None	N
T/R	0.0985	likely_benign	0.1029	benign	-0.142	Destabilizing	0.004	N	0.331	neutral	N	0.436737279	None	None	N
T/S	0.1046	likely_benign	0.101	benign	-0.464	Destabilizing	0.334	N	0.455	neutral	N	0.464459811	None	None	N
T/V	0.0922	likely_benign	0.0924	benign	-0.541	Destabilizing	0.766	D	0.333	neutral	None	None	None	None	N
T/W	0.533	ambiguous	0.5379	ambiguous	-1.1	Destabilizing	0.992	D	0.497	neutral	None	None	None	None	N
T/Y	0.2357	likely_benign	0.2266	benign	-0.843	Destabilizing	0.972	D	0.476	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.