TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29160	87703;87704;87705	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
N2AB	27519	82780;82781;82782	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
N2A	26592	79999;80000;80001	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
N2B	20095	60508;60509;60510	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
Novex-1	20220	60883;60884;60885	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
Novex-2	20287	61084;61085;61086	chr2:178557876;178557875;178557874	chr2:179422603;179422602;179422601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-100
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.4099
• 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
E/K	None	None	0.096	N	0.466	0.162	0.216624796971	gnomAD-4.0.0	6.84214E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99425E-07	0	0
E/Q	rs1559260637	None	0.001	N	0.171	0.072	0.254761474806	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
E/Q	rs1559260637	None	0.001	N	0.171	0.072	0.254761474806	gnomAD-4.0.0	4.10529E-06	None	None	None	None	N	None	0	0	None	3.82643E-05	0	None	0	1.73491E-04	1.79885E-06	0	3.31301E-05

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
E/A	0.0965	likely_benign	0.1002	benign	-0.677	Destabilizing	0.042	N	0.446	neutral	N	0.494932725	None	None	N
E/C	0.6018	likely_pathogenic	0.6015	pathogenic	-0.147	Destabilizing	0.958	D	0.573	neutral	None	None	None	None	N
E/D	0.0878	likely_benign	0.0984	benign	-0.666	Destabilizing	0.001	N	0.177	neutral	N	0.436961857	None	None	N
E/F	0.5069	ambiguous	0.5185	ambiguous	-0.532	Destabilizing	0.002	N	0.413	neutral	None	None	None	None	N
E/G	0.0899	likely_benign	0.0978	benign	-0.934	Destabilizing	0.175	N	0.553	neutral	N	0.510710254	None	None	N
E/H	0.3113	likely_benign	0.3015	benign	-0.613	Destabilizing	0.497	N	0.575	neutral	None	None	None	None	N
E/I	0.2403	likely_benign	0.2543	benign	-0.012	Destabilizing	0.124	N	0.587	neutral	None	None	None	None	N
E/K	0.1246	likely_benign	0.1246	benign	-0.108	Destabilizing	0.096	N	0.466	neutral	N	0.43996209	None	None	N
E/L	0.165	likely_benign	0.1629	benign	-0.012	Destabilizing	None	N	0.429	neutral	None	None	None	None	N
E/M	0.2339	likely_benign	0.253	benign	0.309	Stabilizing	0.497	N	0.589	neutral	None	None	None	None	N
E/N	0.1251	likely_benign	0.1373	benign	-0.394	Destabilizing	0.22	N	0.521	neutral	None	None	None	None	N
E/P	0.7376	likely_pathogenic	0.7214	pathogenic	-0.213	Destabilizing	0.667	D	0.659	neutral	None	None	None	None	N
E/Q	0.0958	likely_benign	0.0932	benign	-0.347	Destabilizing	0.001	N	0.171	neutral	N	0.461742872	None	None	N
E/R	0.2216	likely_benign	0.2118	benign	0.077	Stabilizing	0.124	N	0.525	neutral	None	None	None	None	N
E/S	0.1188	likely_benign	0.1297	benign	-0.609	Destabilizing	0.124	N	0.464	neutral	None	None	None	None	N
E/T	0.1542	likely_benign	0.1656	benign	-0.408	Destabilizing	0.22	N	0.51	neutral	None	None	None	None	N
E/V	0.1518	likely_benign	0.1625	benign	-0.213	Destabilizing	0.096	N	0.541	neutral	N	0.516193432	None	None	N
E/W	0.7974	likely_pathogenic	0.7794	pathogenic	-0.361	Destabilizing	0.958	D	0.568	neutral	None	None	None	None	N
E/Y	0.3864	ambiguous	0.3902	ambiguous	-0.297	Destabilizing	0.331	N	0.662	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.