TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5587	16984;16985;16986	chr2:178732210;178732209;178732208	chr2:179596937;179596936;179596935
N2AB	5270	16033;16034;16035	chr2:178732210;178732209;178732208	chr2:179596937;179596936;179596935
N2A	4343	13252;13253;13254	chr2:178732210;178732209;178732208	chr2:179596937;179596936;179596935
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-39
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.1823
• 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
S/G	rs2080667352	None	None	N	0.185	0.091	0.0806252709748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.169	likely_benign	0.1809	benign	-0.436	Destabilizing	0.035	N	0.463	neutral	None	None	None	None	N
S/C	0.2024	likely_benign	0.2213	benign	-0.233	Destabilizing	0.915	D	0.387	neutral	N	0.506947595	None	None	N
S/D	0.2732	likely_benign	0.3006	benign	-0.149	Destabilizing	None	N	0.2	neutral	None	None	None	None	N
S/E	0.6806	likely_pathogenic	0.7068	pathogenic	-0.23	Destabilizing	0.081	N	0.419	neutral	None	None	None	None	N
S/F	0.4057	ambiguous	0.4217	ambiguous	-0.907	Destabilizing	0.791	D	0.437	neutral	None	None	None	None	N
S/G	0.0731	likely_benign	0.0828	benign	-0.585	Destabilizing	None	N	0.185	neutral	N	0.46588675	None	None	N
S/H	0.4991	ambiguous	0.5297	ambiguous	-1.079	Destabilizing	0.935	D	0.35	neutral	None	None	None	None	N
S/I	0.3812	ambiguous	0.4056	ambiguous	-0.166	Destabilizing	0.484	N	0.427	neutral	N	0.498300314	None	None	N
S/K	0.807	likely_pathogenic	0.8311	pathogenic	-0.666	Destabilizing	0.149	N	0.422	neutral	None	None	None	None	N
S/L	0.2045	likely_benign	0.2165	benign	-0.166	Destabilizing	0.38	N	0.395	neutral	None	None	None	None	N
S/M	0.3577	ambiguous	0.382	ambiguous	0.156	Stabilizing	0.935	D	0.369	neutral	None	None	None	None	N
S/N	0.1166	likely_benign	0.1244	benign	-0.373	Destabilizing	0.117	N	0.453	neutral	N	0.455264495	None	None	N
S/P	0.7624	likely_pathogenic	0.8173	pathogenic	-0.225	Destabilizing	0.555	D	0.335	neutral	None	None	None	None	N
S/Q	0.7175	likely_pathogenic	0.7457	pathogenic	-0.63	Destabilizing	0.555	D	0.395	neutral	None	None	None	None	N
S/R	0.7569	likely_pathogenic	0.7848	pathogenic	-0.401	Destabilizing	0.484	N	0.334	neutral	N	0.48033419	None	None	N
S/T	0.099	likely_benign	0.0973	benign	-0.443	Destabilizing	0.117	N	0.463	neutral	N	0.463102081	None	None	N
S/V	0.3979	ambiguous	0.4194	ambiguous	-0.225	Destabilizing	0.555	D	0.387	neutral	None	None	None	None	N
S/W	0.5871	likely_pathogenic	0.6284	pathogenic	-0.912	Destabilizing	0.935	D	0.58	neutral	None	None	None	None	N
S/Y	0.3392	likely_benign	0.3564	ambiguous	-0.656	Destabilizing	0.791	D	0.426	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.