TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29457	88594;88595;88596	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
N2AB	27816	83671;83672;83673	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
N2A	26889	80890;80891;80892	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
N2B	20392	61399;61400;61401	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
Novex-1	20517	61774;61775;61776	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
Novex-2	20584	61975;61976;61977	chr2:178555090;178555089;178555088	chr2:179419817;179419816;179419815
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-146
• Domain position: 14
• Structural Position: 26
• Q(SASA): 0.4222
• 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/T	rs1436729159	None	0.016	N	0.167	0.064	0.124217242631	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92901E-04	None	0	0	0	0	0
S/T	rs1436729159	None	0.016	N	0.167	0.064	0.124217242631	gnomAD-4.0.0	6.5722E-06	None	None	None	None	N	None	0	0	None	0	1.92901E-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
S/A	0.0665	likely_benign	0.066	benign	-0.592	Destabilizing	0.002	N	0.145	neutral	N	0.476701176	None	None	N
S/C	0.1234	likely_benign	0.125	benign	-0.404	Destabilizing	0.97	D	0.399	neutral	N	0.472901451	None	None	N
S/D	0.4352	ambiguous	0.4223	ambiguous	0.464	Stabilizing	0.002	N	0.143	neutral	None	None	None	None	N
S/E	0.5586	ambiguous	0.5594	ambiguous	0.426	Stabilizing	0.25	N	0.32	neutral	None	None	None	None	N
S/F	0.275	likely_benign	0.2568	benign	-0.992	Destabilizing	0.896	D	0.439	neutral	N	0.472647961	None	None	N
S/G	0.1143	likely_benign	0.1173	benign	-0.778	Destabilizing	0.25	N	0.35	neutral	None	None	None	None	N
S/H	0.4362	ambiguous	0.4393	ambiguous	-1.19	Destabilizing	0.92	D	0.405	neutral	None	None	None	None	N
S/I	0.1772	likely_benign	0.1822	benign	-0.219	Destabilizing	0.85	D	0.461	neutral	None	None	None	None	N
S/K	0.7343	likely_pathogenic	0.719	pathogenic	-0.396	Destabilizing	0.617	D	0.296	neutral	None	None	None	None	N
S/L	0.1142	likely_benign	0.109	benign	-0.219	Destabilizing	0.447	N	0.442	neutral	None	None	None	None	N
S/M	0.1988	likely_benign	0.2025	benign	-0.06	Destabilizing	0.972	D	0.404	neutral	None	None	None	None	N
S/N	0.1504	likely_benign	0.1594	benign	-0.277	Destabilizing	0.021	N	0.188	neutral	None	None	None	None	N
S/P	0.1414	likely_benign	0.1455	benign	-0.312	Destabilizing	0.712	D	0.449	neutral	N	0.440375017	None	None	N
S/Q	0.5458	ambiguous	0.5503	ambiguous	-0.419	Destabilizing	0.92	D	0.379	neutral	None	None	None	None	N
S/R	0.6749	likely_pathogenic	0.6525	pathogenic	-0.295	Destabilizing	0.85	D	0.445	neutral	None	None	None	None	N
S/T	0.0771	likely_benign	0.0768	benign	-0.392	Destabilizing	0.016	N	0.167	neutral	N	0.44599148	None	None	N
S/V	0.1538	likely_benign	0.1546	benign	-0.312	Destabilizing	0.447	N	0.429	neutral	None	None	None	None	N
S/W	0.4459	ambiguous	0.3996	ambiguous	-0.958	Destabilizing	0.992	D	0.557	neutral	None	None	None	None	N
S/Y	0.2526	likely_benign	0.2357	benign	-0.678	Destabilizing	0.963	D	0.433	neutral	N	0.472647961	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.