TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15917	47974;47975;47976	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
N2AB	14276	43051;43052;43053	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
N2A	13349	40270;40271;40272	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
N2B	6852	20779;20780;20781	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
Novex-1	6977	21154;21155;21156	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
Novex-2	7044	21355;21356;21357	chr2:178617336;178617335;178617334	chr2:179482063;179482062;179482061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-3
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1473
• 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
L/Q	None	None	1.0	N	0.801	0.479	0.704706922069	gnomAD-4.0.0	3.38924E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	3.21543E-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
L/A	0.3741	ambiguous	0.3616	ambiguous	-1.832	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
L/C	0.4975	ambiguous	0.4075	ambiguous	-0.907	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
L/D	0.7674	likely_pathogenic	0.7541	pathogenic	-1.746	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
L/E	0.4522	ambiguous	0.4371	ambiguous	-1.589	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
L/F	0.3518	ambiguous	0.3676	ambiguous	-1.096	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
L/G	0.5863	likely_pathogenic	0.5722	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
L/H	0.3941	ambiguous	0.396	ambiguous	-1.543	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
L/I	0.1901	likely_benign	0.202	benign	-0.591	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
L/K	0.2334	likely_benign	0.2238	benign	-1.251	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
L/M	0.1338	likely_benign	0.1362	benign	-0.417	Destabilizing	1.0	D	0.68	prob.neutral	N	0.486724873	None	None	I
L/N	0.3374	likely_benign	0.3237	benign	-1.438	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
L/P	0.3562	ambiguous	0.307	benign	-0.981	Destabilizing	1.0	D	0.826	deleterious	N	0.45738482	None	None	I
L/Q	0.1876	likely_benign	0.192	benign	-1.405	Destabilizing	1.0	D	0.801	deleterious	N	0.450393571	None	None	I
L/R	0.1945	likely_benign	0.1937	benign	-0.888	Destabilizing	1.0	D	0.797	deleterious	N	0.45493756	None	None	I
L/S	0.4731	ambiguous	0.4688	ambiguous	-2.074	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
L/T	0.2006	likely_benign	0.1886	benign	-1.783	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
L/V	0.1521	likely_benign	0.1552	benign	-0.981	Destabilizing	0.999	D	0.543	neutral	N	0.46647584	None	None	I
L/W	0.4803	ambiguous	0.4857	ambiguous	-1.395	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
L/Y	0.5185	ambiguous	0.5237	ambiguous	-1.047	Destabilizing	1.0	D	0.767	deleterious	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.