TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29186	87781;87782;87783	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
N2AB	27545	82858;82859;82860	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
N2A	26618	80077;80078;80079	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
N2B	20121	60586;60587;60588	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
Novex-1	20246	60961;60962;60963	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
Novex-2	20313	61162;61163;61164	chr2:178557798;178557797;178557796	chr2:179422525;179422524;179422523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-100
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.4321
• 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
T/I	rs755409023	None	None	N	0.175	0.125	0.273938319068	gnomAD-4.0.0	6.00161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56251E-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
T/A	0.0727	likely_benign	0.0796	benign	-0.538	Destabilizing	None	N	0.089	neutral	N	0.466916618	None	None	N
T/C	0.2261	likely_benign	0.254	benign	-0.433	Destabilizing	0.356	N	0.336	neutral	None	None	None	None	N
T/D	0.2972	likely_benign	0.3614	ambiguous	0.268	Stabilizing	0.038	N	0.322	neutral	None	None	None	None	N
T/E	0.2073	likely_benign	0.2532	benign	0.264	Stabilizing	0.038	N	0.316	neutral	None	None	None	None	N
T/F	0.198	likely_benign	0.2214	benign	-0.702	Destabilizing	0.072	N	0.361	neutral	None	None	None	None	N
T/G	0.1692	likely_benign	0.2015	benign	-0.768	Destabilizing	0.016	N	0.292	neutral	None	None	None	None	N
T/H	0.1764	likely_benign	0.201	benign	-0.937	Destabilizing	0.356	N	0.328	neutral	None	None	None	None	N
T/I	0.118	likely_benign	0.1372	benign	-0.03	Destabilizing	None	N	0.175	neutral	N	0.456123621	None	None	N
T/K	0.1762	likely_benign	0.2002	benign	-0.483	Destabilizing	0.038	N	0.321	neutral	None	None	None	None	N
T/L	0.082	likely_benign	0.0841	benign	-0.03	Destabilizing	0.007	N	0.238	neutral	None	None	None	None	N
T/M	0.0715	likely_benign	0.071	benign	-0.061	Destabilizing	0.003	N	0.219	neutral	None	None	None	None	N
T/N	0.0858	likely_benign	0.0963	benign	-0.454	Destabilizing	0.029	N	0.223	neutral	N	0.48615574	None	None	N
T/P	0.5275	ambiguous	0.5818	pathogenic	-0.167	Destabilizing	0.055	N	0.372	neutral	N	0.470065338	None	None	N
T/Q	0.1583	likely_benign	0.1814	benign	-0.539	Destabilizing	0.072	N	0.371	neutral	None	None	None	None	N
T/R	0.1601	likely_benign	0.169	benign	-0.282	Destabilizing	0.072	N	0.371	neutral	None	None	None	None	N
T/S	0.086	likely_benign	0.0939	benign	-0.728	Destabilizing	None	N	0.099	neutral	N	0.43295876	None	None	N
T/V	0.0948	likely_benign	0.1052	benign	-0.167	Destabilizing	0.007	N	0.167	neutral	None	None	None	None	N
T/W	0.4624	ambiguous	0.4893	ambiguous	-0.706	Destabilizing	0.864	D	0.326	neutral	None	None	None	None	N
T/Y	0.2121	likely_benign	0.2362	benign	-0.43	Destabilizing	0.356	N	0.396	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.