TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29207	87844;87845;87846	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
N2AB	27566	82921;82922;82923	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
N2A	26639	80140;80141;80142	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
N2B	20142	60649;60650;60651	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
Novex-1	20267	61024;61025;61026	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
Novex-2	20334	61225;61226;61227	chr2:178557735;178557734;178557733	chr2:179422462;179422461;179422460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-100
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3189
• 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	rs1403726987	-0.815	0.805	N	0.503	0.294	0.369495900351	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1403726987	-0.815	0.805	N	0.503	0.294	0.369495900351	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1403726987	-0.815	0.805	N	0.503	0.294	0.369495900351	gnomAD-4.0.0	4.95735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.7807E-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
E/A	0.3052	likely_benign	0.2976	benign	-0.932	Destabilizing	0.892	D	0.591	neutral	N	0.491830124	None	None	N
E/C	0.936	likely_pathogenic	0.9335	pathogenic	-0.422	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/D	0.3968	ambiguous	0.3988	ambiguous	-1.131	Destabilizing	0.025	N	0.283	neutral	N	0.481777265	None	None	N
E/F	0.9534	likely_pathogenic	0.9485	pathogenic	-0.531	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/G	0.5461	ambiguous	0.517	ambiguous	-1.293	Destabilizing	0.892	D	0.696	prob.neutral	N	0.492590593	None	None	N
E/H	0.8387	likely_pathogenic	0.8315	pathogenic	-0.842	Destabilizing	0.997	D	0.676	prob.neutral	None	None	None	None	N
E/I	0.5415	ambiguous	0.5429	ambiguous	0.054	Stabilizing	0.987	D	0.818	deleterious	None	None	None	None	N
E/K	0.4246	ambiguous	0.4046	ambiguous	-0.537	Destabilizing	0.805	D	0.503	neutral	N	0.478939655	None	None	N
E/L	0.7265	likely_pathogenic	0.7091	pathogenic	0.054	Stabilizing	0.987	D	0.797	deleterious	None	None	None	None	N
E/M	0.6373	likely_pathogenic	0.6307	pathogenic	0.566	Stabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
E/N	0.5629	ambiguous	0.5606	ambiguous	-0.984	Destabilizing	0.95	D	0.666	neutral	None	None	None	None	N
E/P	0.8706	likely_pathogenic	0.8793	pathogenic	-0.254	Destabilizing	0.987	D	0.811	deleterious	None	None	None	None	N
E/Q	0.2362	likely_benign	0.2194	benign	-0.858	Destabilizing	0.426	N	0.219	neutral	D	0.523964766	None	None	N
E/R	0.6233	likely_pathogenic	0.6024	pathogenic	-0.349	Destabilizing	0.975	D	0.669	neutral	None	None	None	None	N
E/S	0.4452	ambiguous	0.4298	ambiguous	-1.318	Destabilizing	0.916	D	0.546	neutral	None	None	None	None	N
E/T	0.3547	ambiguous	0.3538	ambiguous	-1.011	Destabilizing	0.975	D	0.762	deleterious	None	None	None	None	N
E/V	0.3577	ambiguous	0.3557	ambiguous	-0.254	Destabilizing	0.983	D	0.787	deleterious	N	0.483298202	None	None	N
E/W	0.9873	likely_pathogenic	0.9866	pathogenic	-0.304	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/Y	0.9111	likely_pathogenic	0.9014	pathogenic	-0.269	Destabilizing	0.996	D	0.797	deleterious	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.