TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29268	88027;88028;88029	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
N2AB	27627	83104;83105;83106	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
N2A	26700	80323;80324;80325	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
N2B	20203	60832;60833;60834	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
Novex-1	20328	61207;61208;61209	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
Novex-2	20395	61408;61409;61410	chr2:178557460;178557459;178557458	chr2:179422187;179422186;179422185
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-101
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5541
• 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
A/T	None	None	0.062	N	0.264	0.058	0.119812018005	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
A/C	0.2852	likely_benign	0.3951	ambiguous	-0.733	Destabilizing	0.935	D	0.363	neutral	None	None	None	None	I
A/D	0.1677	likely_benign	0.2216	benign	-0.447	Destabilizing	0.149	N	0.405	neutral	None	None	None	None	I
A/E	0.1597	likely_benign	0.2014	benign	-0.609	Destabilizing	0.117	N	0.334	neutral	N	0.451003016	None	None	I
A/F	0.239	likely_benign	0.3358	benign	-0.923	Destabilizing	0.555	D	0.495	neutral	None	None	None	None	I
A/G	0.1304	likely_benign	0.1615	benign	-0.259	Destabilizing	0.027	N	0.251	neutral	N	0.504320213	None	None	I
A/H	0.2667	likely_benign	0.3557	ambiguous	-0.315	Destabilizing	0.001	N	0.297	neutral	None	None	None	None	I
A/I	0.1285	likely_benign	0.1853	benign	-0.349	Destabilizing	0.081	N	0.402	neutral	None	None	None	None	I
A/K	0.2569	likely_benign	0.3378	benign	-0.516	Destabilizing	0.081	N	0.411	neutral	None	None	None	None	I
A/L	0.0921	likely_benign	0.1225	benign	-0.349	Destabilizing	0.081	N	0.334	neutral	None	None	None	None	I
A/M	0.1251	likely_benign	0.175	benign	-0.339	Destabilizing	0.555	D	0.419	neutral	None	None	None	None	I
A/N	0.1325	likely_benign	0.1814	benign	-0.214	Destabilizing	0.081	N	0.429	neutral	None	None	None	None	I
A/P	0.0639	likely_benign	0.0835	benign	-0.278	Destabilizing	None	N	0.233	neutral	N	0.347318501	None	None	I
A/Q	0.1788	likely_benign	0.2354	benign	-0.513	Destabilizing	0.38	N	0.457	neutral	None	None	None	None	I
A/R	0.2579	likely_benign	0.322	benign	-0.058	Destabilizing	0.38	N	0.433	neutral	None	None	None	None	I
A/S	0.079	likely_benign	0.0896	benign	-0.402	Destabilizing	0.002	N	0.182	neutral	N	0.44985101	None	None	I
A/T	0.0676	likely_benign	0.0823	benign	-0.488	Destabilizing	0.062	N	0.264	neutral	N	0.45685434	None	None	I
A/V	0.0799	likely_benign	0.1028	benign	-0.278	Destabilizing	0.002	N	0.238	neutral	N	0.470697221	None	None	I
A/W	0.5523	ambiguous	0.6835	pathogenic	-1.046	Destabilizing	0.935	D	0.577	neutral	None	None	None	None	I
A/Y	0.3223	likely_benign	0.4282	ambiguous	-0.692	Destabilizing	0.38	N	0.487	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.