TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6540	19843;19844;19845	chr2:178728206;178728205;178728204	chr2:179592933;179592932;179592931
N2AB	6223	18892;18893;18894	chr2:178728206;178728205;178728204	chr2:179592933;179592932;179592931
N2A	5296	16111;16112;16113	chr2:178728206;178728205;178728204	chr2:179592933;179592932;179592931
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-49
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0825
• 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
V/A	rs1045155829	None	None	N	0.333	0.366	0.492475246742	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	5.50964E-04	None	0	0	0	0	0
V/I	rs1157784163	-0.48	None	N	0.273	0.133	0.165133752707	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
V/I	rs1157784163	-0.48	None	N	0.273	0.133	0.165133752707	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1157784163	-0.48	None	N	0.273	0.133	0.165133752707	gnomAD-4.0.0	1.24006E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69581E-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
V/A	0.526	ambiguous	0.5708	pathogenic	-2.317	Highly Destabilizing	None	N	0.333	neutral	N	0.501016016	None	None	N
V/C	0.901	likely_pathogenic	0.8955	pathogenic	-2.149	Highly Destabilizing	0.628	D	0.763	deleterious	None	None	None	None	N
V/D	0.8955	likely_pathogenic	0.9041	pathogenic	-3.427	Highly Destabilizing	0.295	N	0.799	deleterious	D	0.524489095	None	None	N
V/E	0.8355	likely_pathogenic	0.8365	pathogenic	-3.134	Highly Destabilizing	0.072	N	0.77	deleterious	None	None	None	None	N
V/F	0.3001	likely_benign	0.2895	benign	-1.243	Destabilizing	0.055	N	0.713	prob.delet.	N	0.513647064	None	None	N
V/G	0.5895	likely_pathogenic	0.6137	pathogenic	-2.914	Highly Destabilizing	0.029	N	0.725	prob.delet.	D	0.524489095	None	None	N
V/H	0.9444	likely_pathogenic	0.9357	pathogenic	-2.813	Highly Destabilizing	0.864	D	0.836	deleterious	None	None	None	None	N
V/I	0.0837	likely_benign	0.0859	benign	-0.595	Destabilizing	None	N	0.273	neutral	N	0.372059443	None	None	N
V/K	0.8761	likely_pathogenic	0.8525	pathogenic	-1.927	Destabilizing	0.072	N	0.74	deleterious	None	None	None	None	N
V/L	0.2739	likely_benign	0.2891	benign	-0.595	Destabilizing	None	N	0.279	neutral	N	0.418117885	None	None	N
V/M	0.2276	likely_benign	0.2373	benign	-0.983	Destabilizing	0.007	N	0.383	neutral	None	None	None	None	N
V/N	0.8342	likely_pathogenic	0.8461	pathogenic	-2.547	Highly Destabilizing	0.356	N	0.829	deleterious	None	None	None	None	N
V/P	0.9713	likely_pathogenic	0.9752	pathogenic	-1.148	Destabilizing	0.356	N	0.789	deleterious	None	None	None	None	N
V/Q	0.8751	likely_pathogenic	0.8574	pathogenic	-2.234	Highly Destabilizing	0.356	N	0.814	deleterious	None	None	None	None	N
V/R	0.8607	likely_pathogenic	0.8337	pathogenic	-1.939	Destabilizing	0.356	N	0.814	deleterious	None	None	None	None	N
V/S	0.7668	likely_pathogenic	0.7903	pathogenic	-3.09	Highly Destabilizing	0.038	N	0.702	prob.neutral	None	None	None	None	N
V/T	0.6776	likely_pathogenic	0.7016	pathogenic	-2.642	Highly Destabilizing	0.072	N	0.549	neutral	None	None	None	None	N
V/W	0.9221	likely_pathogenic	0.9109	pathogenic	-1.888	Destabilizing	0.864	D	0.831	deleterious	None	None	None	None	N
V/Y	0.7882	likely_pathogenic	0.7657	pathogenic	-1.558	Destabilizing	0.356	N	0.743	deleterious	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.