TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5593	17002;17003;17004	chr2:178732192;178732191;178732190	chr2:179596919;179596918;179596917
N2AB	5276	16051;16052;16053	chr2:178732192;178732191;178732190	chr2:179596919;179596918;179596917
N2A	4349	13270;13271;13272	chr2:178732192;178732191;178732190	chr2:179596919;179596918;179596917
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-39
• Domain position: 51
• Structural Position: 125
• Q(SASA): 0.3968
• 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/A	None	None	0.061	N	0.11	0.104	0.156986980423	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	2.98811E-05	0	None	0	0	None	0	0	8.99459E-07	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	0.089	likely_benign	0.0953	benign	-0.559	Destabilizing	0.061	N	0.11	neutral	N	0.499522974	None	None	N
S/C	0.144	likely_benign	0.1682	benign	-0.301	Destabilizing	0.999	D	0.423	neutral	D	0.530463349	None	None	N
S/D	0.2519	likely_benign	0.2915	benign	-0.014	Destabilizing	0.884	D	0.35	neutral	None	None	None	None	N
S/E	0.3792	ambiguous	0.4076	ambiguous	-0.015	Destabilizing	0.939	D	0.363	neutral	None	None	None	None	N
S/F	0.1475	likely_benign	0.1751	benign	-0.727	Destabilizing	0.996	D	0.535	neutral	N	0.49400135	None	None	N
S/G	0.1217	likely_benign	0.1361	benign	-0.813	Destabilizing	0.759	D	0.364	neutral	None	None	None	None	N
S/H	0.2647	likely_benign	0.2986	benign	-1.297	Destabilizing	0.991	D	0.437	neutral	None	None	None	None	N
S/I	0.1559	likely_benign	0.1689	benign	0.005	Stabilizing	0.991	D	0.49	neutral	None	None	None	None	N
S/K	0.5943	likely_pathogenic	0.6499	pathogenic	-0.623	Destabilizing	0.939	D	0.354	neutral	None	None	None	None	N
S/L	0.1047	likely_benign	0.1148	benign	0.005	Stabilizing	0.939	D	0.448	neutral	None	None	None	None	N
S/M	0.2005	likely_benign	0.2138	benign	0.138	Stabilizing	0.999	D	0.425	neutral	None	None	None	None	N
S/N	0.1276	likely_benign	0.1427	benign	-0.524	Destabilizing	0.17	N	0.182	neutral	None	None	None	None	N
S/P	0.8274	likely_pathogenic	0.8696	pathogenic	-0.148	Destabilizing	0.988	D	0.395	neutral	D	0.523208421	None	None	N
S/Q	0.4307	ambiguous	0.4687	ambiguous	-0.603	Destabilizing	0.991	D	0.396	neutral	None	None	None	None	N
S/R	0.4825	ambiguous	0.5431	ambiguous	-0.578	Destabilizing	0.991	D	0.388	neutral	None	None	None	None	N
S/T	0.0772	likely_benign	0.0788	benign	-0.512	Destabilizing	0.826	D	0.449	neutral	N	0.488073829	None	None	N
S/V	0.1656	likely_benign	0.1807	benign	-0.148	Destabilizing	0.939	D	0.452	neutral	None	None	None	None	N
S/W	0.2615	likely_benign	0.3223	benign	-0.766	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
S/Y	0.1371	likely_benign	0.1577	benign	-0.484	Destabilizing	0.996	D	0.527	neutral	N	0.495976359	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.