TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8093	24502;24503;24504	chr2:178718923;178718922;178718921	chr2:179583650;179583649;179583648
N2AB	7776	23551;23552;23553	chr2:178718923;178718922;178718921	chr2:179583650;179583649;179583648
N2A	6849	20770;20771;20772	chr2:178718923;178718922;178718921	chr2:179583650;179583649;179583648
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-66
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.5031
• Predicted PPI site: I

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
M/T	rs773993718	0.088	None	N	0.164	0.084	0.136095386433	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.98E-06	0
M/T	rs773993718	0.088	None	N	0.164	0.084	0.136095386433	gnomAD-4.0.0	1.59434E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41663E-04	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
M/A	0.1692	likely_benign	0.1815	benign	-0.827	Destabilizing	None	N	0.168	neutral	None	None	None	None	I
M/C	0.623	likely_pathogenic	0.6491	pathogenic	-0.822	Destabilizing	0.132	N	0.267	neutral	None	None	None	None	I
M/D	0.3791	ambiguous	0.4367	ambiguous	0.388	Stabilizing	0.009	N	0.346	neutral	None	None	None	None	I
M/E	0.1756	likely_benign	0.1927	benign	0.386	Stabilizing	0.002	N	0.295	neutral	None	None	None	None	I
M/F	0.2349	likely_benign	0.2377	benign	-0.107	Destabilizing	0.009	N	0.194	neutral	None	None	None	None	I
M/G	0.3176	likely_benign	0.3359	benign	-1.087	Destabilizing	None	N	0.182	neutral	None	None	None	None	I
M/H	0.2356	likely_benign	0.272	benign	-0.182	Destabilizing	0.316	N	0.343	neutral	None	None	None	None	I
M/I	0.2267	likely_benign	0.227	benign	-0.206	Destabilizing	None	N	0.133	neutral	N	0.475447596	None	None	I
M/K	0.0844	likely_benign	0.0947	benign	0.189	Stabilizing	None	N	0.195	neutral	N	0.411761476	None	None	I
M/L	0.1173	likely_benign	0.1176	benign	-0.206	Destabilizing	None	N	0.174	neutral	N	0.494129357	None	None	I
M/N	0.1825	likely_benign	0.2049	benign	0.264	Stabilizing	0.009	N	0.301	neutral	None	None	None	None	I
M/P	0.831	likely_pathogenic	0.8478	pathogenic	-0.382	Destabilizing	0.018	N	0.302	neutral	None	None	None	None	I
M/Q	0.1107	likely_benign	0.1219	benign	0.19	Stabilizing	0.009	N	0.183	neutral	None	None	None	None	I
M/R	0.0928	likely_benign	0.1054	benign	0.606	Stabilizing	0.003	N	0.295	neutral	N	0.441180306	None	None	I
M/S	0.1378	likely_benign	0.1564	benign	-0.327	Destabilizing	None	N	0.165	neutral	None	None	None	None	I
M/T	0.085	likely_benign	0.0967	benign	-0.21	Destabilizing	None	N	0.164	neutral	N	0.398005532	None	None	I
M/V	0.0869	likely_benign	0.0876	benign	-0.382	Destabilizing	None	N	0.102	neutral	N	0.512715118	None	None	I
M/W	0.4822	ambiguous	0.5257	ambiguous	-0.081	Destabilizing	0.316	N	0.261	neutral	None	None	None	None	I
M/Y	0.341	ambiguous	0.3878	ambiguous	0.013	Stabilizing	0.041	N	0.372	neutral	None	None	None	None	I

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.