TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29365	88318;88319;88320	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
N2AB	27724	83395;83396;83397	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
N2A	26797	80614;80615;80616	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
N2B	20300	61123;61124;61125	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
Novex-1	20425	61498;61499;61500	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
Novex-2	20492	61699;61700;61701	chr2:178557061;178557060;178557059	chr2:179421788;179421787;179421786
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: Fn3-102
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2438
• 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
S/G	rs1207057627	None	0.565	N	0.623	0.197	0.220303561663	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1875	likely_benign	0.1329	benign	-0.547	Destabilizing	0.587	D	0.646	neutral	None	None	None	None	I
S/C	0.1517	likely_benign	0.1036	benign	-0.285	Destabilizing	0.995	D	0.621	neutral	N	0.496731649	None	None	I
S/D	0.9623	likely_pathogenic	0.9268	pathogenic	-0.227	Destabilizing	0.633	D	0.649	neutral	None	None	None	None	I
S/E	0.9547	likely_pathogenic	0.9313	pathogenic	-0.314	Destabilizing	0.775	D	0.663	neutral	None	None	None	None	I
S/F	0.6228	likely_pathogenic	0.4027	ambiguous	-1.117	Destabilizing	0.987	D	0.669	neutral	None	None	None	None	I
S/G	0.3367	likely_benign	0.209	benign	-0.675	Destabilizing	0.565	D	0.623	neutral	N	0.481187245	None	None	I
S/H	0.7624	likely_pathogenic	0.687	pathogenic	-1.242	Destabilizing	0.979	D	0.605	neutral	None	None	None	None	I
S/I	0.7457	likely_pathogenic	0.5903	pathogenic	-0.332	Destabilizing	0.949	D	0.669	neutral	N	0.510605942	None	None	I
S/K	0.9853	likely_pathogenic	0.9739	pathogenic	-0.601	Destabilizing	0.633	D	0.667	neutral	None	None	None	None	I
S/L	0.3958	ambiguous	0.2298	benign	-0.332	Destabilizing	0.961	D	0.671	neutral	None	None	None	None	I
S/M	0.5287	ambiguous	0.3882	ambiguous	0.158	Stabilizing	0.996	D	0.607	neutral	None	None	None	None	I
S/N	0.6621	likely_pathogenic	0.4981	ambiguous	-0.361	Destabilizing	0.008	N	0.456	neutral	N	0.506326755	None	None	I
S/P	0.9819	likely_pathogenic	0.9656	pathogenic	-0.375	Destabilizing	0.011	N	0.476	neutral	None	None	None	None	I
S/Q	0.8813	likely_pathogenic	0.8288	pathogenic	-0.684	Destabilizing	0.923	D	0.659	neutral	None	None	None	None	I
S/R	0.9728	likely_pathogenic	0.9464	pathogenic	-0.335	Destabilizing	0.901	D	0.625	neutral	N	0.499855067	None	None	I
S/T	0.4141	ambiguous	0.2808	benign	-0.457	Destabilizing	0.722	D	0.653	neutral	N	0.49076694	None	None	I
S/V	0.6487	likely_pathogenic	0.4982	ambiguous	-0.375	Destabilizing	0.961	D	0.659	neutral	None	None	None	None	I
S/W	0.7238	likely_pathogenic	0.6012	pathogenic	-1.083	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	I
S/Y	0.5473	ambiguous	0.394	ambiguous	-0.823	Destabilizing	0.987	D	0.669	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.