TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7093	21502;21503;21504	chr2:178723982;178723981;178723980	chr2:179588709;179588708;179588707
N2AB	6776	20551;20552;20553	chr2:178723982;178723981;178723980	chr2:179588709;179588708;179588707
N2A	5849	17770;17771;17772	chr2:178723982;178723981;178723980	chr2:179588709;179588708;179588707
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-55
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.4668
• 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	rs773883340	-0.535	0.027	N	0.318	0.164	0.208816687407	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.2299E-04	None	0	None	0	0	0
T/A	rs773883340	-0.535	0.027	N	0.318	0.164	0.208816687407	gnomAD-4.0.0	9.55122E-06	None	None	None	None	N	None	0	0	None	0	1.66445E-04	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
T/A	0.0678	likely_benign	0.0685	benign	-0.54	Destabilizing	0.027	N	0.318	neutral	N	0.517359373	None	None	N
T/C	0.4186	ambiguous	0.4073	ambiguous	-0.172	Destabilizing	0.935	D	0.426	neutral	None	None	None	None	N
T/D	0.2642	likely_benign	0.2572	benign	-0.048	Destabilizing	0.001	N	0.249	neutral	None	None	None	None	N
T/E	0.2625	likely_benign	0.2565	benign	-0.114	Destabilizing	0.081	N	0.345	neutral	None	None	None	None	N
T/F	0.1867	likely_benign	0.1804	benign	-0.96	Destabilizing	0.38	N	0.513	neutral	None	None	None	None	N
T/G	0.18	likely_benign	0.1837	benign	-0.704	Destabilizing	0.081	N	0.411	neutral	None	None	None	None	N
T/H	0.2019	likely_benign	0.197	benign	-1.082	Destabilizing	0.824	D	0.483	neutral	None	None	None	None	N
T/I	0.1321	likely_benign	0.1268	benign	-0.219	Destabilizing	0.001	N	0.252	neutral	N	0.497640249	None	None	N
T/K	0.1839	likely_benign	0.1917	benign	-0.447	Destabilizing	0.062	N	0.37	neutral	N	0.511028046	None	None	N
T/L	0.097	likely_benign	0.0937	benign	-0.219	Destabilizing	0.012	N	0.338	neutral	None	None	None	None	N
T/M	0.0941	likely_benign	0.0951	benign	0.176	Stabilizing	0.012	N	0.367	neutral	None	None	None	None	N
T/N	0.0959	likely_benign	0.1008	benign	-0.209	Destabilizing	0.081	N	0.357	neutral	None	None	None	None	N
T/P	0.2835	likely_benign	0.331	benign	-0.297	Destabilizing	0.484	N	0.431	neutral	N	0.516157756	None	None	N
T/Q	0.2001	likely_benign	0.1988	benign	-0.487	Destabilizing	0.38	N	0.436	neutral	None	None	None	None	N
T/R	0.1342	likely_benign	0.1363	benign	-0.151	Destabilizing	0.317	N	0.429	neutral	N	0.521938473	None	None	N
T/S	0.077	likely_benign	0.0763	benign	-0.43	Destabilizing	0.002	N	0.248	neutral	N	0.435492925	None	None	N
T/V	0.1114	likely_benign	0.1032	benign	-0.297	Destabilizing	0.012	N	0.339	neutral	None	None	None	None	N
T/W	0.4983	ambiguous	0.493	ambiguous	-0.921	Destabilizing	0.935	D	0.561	neutral	None	None	None	None	N
T/Y	0.2212	likely_benign	0.2225	benign	-0.66	Destabilizing	0.555	D	0.5	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.