TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29153	87682;87683;87684	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
N2AB	27512	82759;82760;82761	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
N2A	26585	79978;79979;79980	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
N2B	20088	60487;60488;60489	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
Novex-1	20213	60862;60863;60864	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
Novex-2	20280	61063;61064;61065	chr2:178557897;178557896;178557895	chr2:179422624;179422623;179422622
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: 17
• Structural Position: 18
• Q(SASA): 0.3709
• 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/G	None	None	0.117	N	0.419	0.195	0.26169431596	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	2.28624E-05	None	0	0	None	0	0	0	0	0
E/K	rs1409902738	0.039	0.062	N	0.449	0.137	0.180583059064	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/K	rs1409902738	0.039	0.062	N	0.449	0.137	0.180583059064	gnomAD-4.0.0	1.36858E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99428E-07	0	1.65651E-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	0.1599	likely_benign	0.1917	benign	-0.854	Destabilizing	0.062	N	0.408	neutral	N	0.499125037	None	None	N
E/C	0.7941	likely_pathogenic	0.8409	pathogenic	-0.192	Destabilizing	0.935	D	0.573	neutral	None	None	None	None	N
E/D	0.0664	likely_benign	0.0816	benign	-0.62	Destabilizing	None	N	0.083	neutral	N	0.362808028	None	None	N
E/F	0.7542	likely_pathogenic	0.8085	pathogenic	-0.618	Destabilizing	0.791	D	0.479	neutral	None	None	None	None	N
E/G	0.1548	likely_benign	0.1713	benign	-1.111	Destabilizing	0.117	N	0.419	neutral	N	0.481808713	None	None	N
E/H	0.5172	ambiguous	0.5698	pathogenic	-0.686	Destabilizing	0.555	D	0.393	neutral	None	None	None	None	N
E/I	0.4791	ambiguous	0.553	ambiguous	-0.179	Destabilizing	0.555	D	0.475	neutral	None	None	None	None	N
E/K	0.2871	likely_benign	0.3105	benign	-0.01	Destabilizing	0.062	N	0.449	neutral	N	0.48486766	None	None	N
E/L	0.4822	ambiguous	0.5499	ambiguous	-0.179	Destabilizing	0.38	N	0.411	neutral	None	None	None	None	N
E/M	0.4921	ambiguous	0.5624	ambiguous	0.202	Stabilizing	0.824	D	0.44	neutral	None	None	None	None	N
E/N	0.1483	likely_benign	0.1903	benign	-0.401	Destabilizing	0.081	N	0.432	neutral	None	None	None	None	N
E/P	0.886	likely_pathogenic	0.9255	pathogenic	-0.384	Destabilizing	0.555	D	0.415	neutral	None	None	None	None	N
E/Q	0.2003	likely_benign	0.2117	benign	-0.363	Destabilizing	0.002	N	0.221	neutral	N	0.505859008	None	None	N
E/R	0.4566	ambiguous	0.4689	ambiguous	0.15	Stabilizing	0.235	N	0.394	neutral	None	None	None	None	N
E/S	0.1632	likely_benign	0.1981	benign	-0.622	Destabilizing	0.081	N	0.397	neutral	None	None	None	None	N
E/T	0.1801	likely_benign	0.2179	benign	-0.407	Destabilizing	0.149	N	0.435	neutral	None	None	None	None	N
E/V	0.2899	likely_benign	0.3378	benign	-0.384	Destabilizing	0.317	N	0.394	neutral	N	0.468241686	None	None	N
E/W	0.9064	likely_pathogenic	0.9259	pathogenic	-0.37	Destabilizing	0.935	D	0.627	neutral	None	None	None	None	N
E/Y	0.5478	ambiguous	0.6115	pathogenic	-0.352	Destabilizing	0.555	D	0.457	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.