TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8460	25603;25604;25605	chr2:178717356;178717355;178717354	chr2:179582083;179582082;179582081
N2AB	8143	24652;24653;24654	chr2:178717356;178717355;178717354	chr2:179582083;179582082;179582081
N2A	7216	21871;21872;21873	chr2:178717356;178717355;178717354	chr2:179582083;179582082;179582081
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-70
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6587
• 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	0.021	N	0.249	0.141	0.598822425987	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.2071	likely_benign	0.1932	benign	-1.707	Destabilizing	0.269	N	0.341	neutral	None	None	None	None	I
L/C	0.4983	ambiguous	0.4626	ambiguous	-0.614	Destabilizing	0.979	D	0.371	neutral	None	None	None	None	I
L/D	0.551	ambiguous	0.5012	ambiguous	-1.525	Destabilizing	0.862	D	0.4	neutral	None	None	None	None	I
L/E	0.1939	likely_benign	0.1769	benign	-1.545	Destabilizing	0.397	N	0.415	neutral	None	None	None	None	I
L/F	0.1333	likely_benign	0.1335	benign	-1.318	Destabilizing	0.713	D	0.332	neutral	None	None	None	None	I
L/G	0.5285	ambiguous	0.4872	ambiguous	-2.007	Highly Destabilizing	0.783	D	0.421	neutral	None	None	None	None	I
L/H	0.1603	likely_benign	0.1513	benign	-1.329	Destabilizing	0.84	D	0.36	neutral	None	None	None	None	I
L/I	0.0646	likely_benign	0.0658	benign	-0.95	Destabilizing	None	N	0.121	neutral	N	0.442821542	None	None	I
L/K	0.1727	likely_benign	0.1563	benign	-1.196	Destabilizing	0.026	N	0.383	neutral	None	None	None	None	I
L/M	0.0906	likely_benign	0.0885	benign	-0.485	Destabilizing	0.427	N	0.384	neutral	None	None	None	None	I
L/N	0.3102	likely_benign	0.2875	benign	-0.863	Destabilizing	0.927	D	0.394	neutral	None	None	None	None	I
L/P	0.8981	likely_pathogenic	0.8547	pathogenic	-1.174	Destabilizing	0.967	D	0.393	neutral	N	0.499253615	None	None	I
L/Q	0.0889	likely_benign	0.0867	benign	-1.093	Destabilizing	0.021	N	0.249	neutral	N	0.45620934	None	None	I
L/R	0.128	likely_benign	0.1196	benign	-0.519	Destabilizing	0.002	N	0.249	neutral	N	0.440858672	None	None	I
L/S	0.2118	likely_benign	0.2014	benign	-1.339	Destabilizing	0.64	D	0.385	neutral	None	None	None	None	I
L/T	0.1539	likely_benign	0.1513	benign	-1.261	Destabilizing	0.348	N	0.374	neutral	None	None	None	None	I
L/V	0.0675	likely_benign	0.064	benign	-1.174	Destabilizing	None	N	0.099	neutral	N	0.439839952	None	None	I
L/W	0.2355	likely_benign	0.2353	benign	-1.433	Destabilizing	0.995	D	0.373	neutral	None	None	None	None	I
L/Y	0.3037	likely_benign	0.2967	benign	-1.244	Destabilizing	0.371	N	0.397	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.