TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8860	26803;26804;26805	chr2:178714080;178714079;178714078	chr2:179578807;179578806;179578805
N2AB	8543	25852;25853;25854	chr2:178714080;178714079;178714078	chr2:179578807;179578806;179578805
N2A	7616	23071;23072;23073	chr2:178714080;178714079;178714078	chr2:179578807;179578806;179578805
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-74
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.307
• 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	None	None	0.014	N	0.291	0.173	0.240491677333	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85871E-06	0	0
S/N	rs1240256366	None	0.007	N	0.321	0.087	0.110078149338	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
S/N	rs1240256366	None	0.007	N	0.321	0.087	0.110078149338	gnomAD-4.0.0	1.97184E-05	None	None	None	None	N	None	7.23903E-05	0	None	0	0	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
S/A	0.0736	likely_benign	0.0753	benign	-0.507	Destabilizing	None	N	0.075	neutral	None	None	None	None	N
S/C	0.1158	likely_benign	0.1369	benign	-0.356	Destabilizing	0.196	N	0.411	neutral	D	0.522616217	None	None	N
S/D	0.2502	likely_benign	0.2584	benign	0.227	Stabilizing	0.018	N	0.304	neutral	None	None	None	None	N
S/E	0.2871	likely_benign	0.2877	benign	0.208	Stabilizing	0.018	N	0.295	neutral	None	None	None	None	N
S/F	0.1118	likely_benign	0.1166	benign	-0.827	Destabilizing	None	N	0.334	neutral	None	None	None	None	N
S/G	0.0979	likely_benign	0.107	benign	-0.721	Destabilizing	0.014	N	0.291	neutral	N	0.503498004	None	None	N
S/H	0.1773	likely_benign	0.1794	benign	-1.115	Destabilizing	None	N	0.267	neutral	None	None	None	None	N
S/I	0.0815	likely_benign	0.0857	benign	-0.057	Destabilizing	None	N	0.273	neutral	N	0.497544248	None	None	N
S/K	0.2758	likely_benign	0.2837	benign	-0.466	Destabilizing	0.009	N	0.271	neutral	None	None	None	None	N
S/L	0.0701	likely_benign	0.072	benign	-0.057	Destabilizing	0.004	N	0.337	neutral	None	None	None	None	N
S/M	0.113	likely_benign	0.1239	benign	-0.018	Destabilizing	0.138	N	0.436	neutral	None	None	None	None	N
S/N	0.0829	likely_benign	0.0901	benign	-0.361	Destabilizing	0.007	N	0.321	neutral	N	0.477630336	None	None	N
S/P	0.4621	ambiguous	0.5012	ambiguous	-0.173	Destabilizing	0.085	N	0.462	neutral	None	None	None	None	N
S/Q	0.2543	likely_benign	0.2596	benign	-0.453	Destabilizing	0.044	N	0.381	neutral	None	None	None	None	N
S/R	0.2335	likely_benign	0.2414	benign	-0.373	Destabilizing	None	N	0.201	neutral	N	0.478803772	None	None	N
S/T	0.0535	likely_benign	0.0585	benign	-0.396	Destabilizing	None	N	0.056	neutral	N	0.446421994	None	None	N
S/V	0.101	likely_benign	0.1091	benign	-0.173	Destabilizing	None	N	0.231	neutral	None	None	None	None	N
S/W	0.2139	likely_benign	0.2454	benign	-0.855	Destabilizing	0.788	D	0.521	neutral	None	None	None	None	N
S/Y	0.1116	likely_benign	0.121	benign	-0.557	Destabilizing	0.022	N	0.541	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.