TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33429	100510;100511;100512	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
N2AB	31788	95587;95588;95589	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
N2A	30861	92806;92807;92808	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
N2B	24364	73315;73316;73317	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
Novex-1	24489	73690;73691;73692	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
Novex-2	24556	73891;73892;73893	chr2:178536462;178536461;178536460	chr2:179401189;179401188;179401187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-131
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0616
• 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
L/P	rs762983936	-1.784	1.0	N	0.923	0.695	0.864991553704	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.11E-06	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	0.9104	likely_pathogenic	0.9305	pathogenic	-2.472	Highly Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
L/C	0.914	likely_pathogenic	0.91	pathogenic	-1.698	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9998	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/E	0.9962	likely_pathogenic	0.9977	pathogenic	-2.876	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/F	0.8146	likely_pathogenic	0.8372	pathogenic	-1.538	Destabilizing	1.0	D	0.818	deleterious	D	0.524283333	None	None	N
L/G	0.9915	likely_pathogenic	0.9943	pathogenic	-3.047	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/H	0.9939	likely_pathogenic	0.9963	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.524536823	None	None	N
L/I	0.1212	likely_benign	0.1363	benign	-0.727	Destabilizing	0.999	D	0.557	neutral	N	0.472895654	None	None	N
L/K	0.9934	likely_pathogenic	0.9965	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/M	0.4225	ambiguous	0.4161	ambiguous	-0.935	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/N	0.9976	likely_pathogenic	0.9986	pathogenic	-2.828	Highly Destabilizing	1.0	D	0.925	deleterious	None	None	None	None	N
L/P	0.9945	likely_pathogenic	0.9975	pathogenic	-1.303	Destabilizing	1.0	D	0.923	deleterious	N	0.513180517	None	None	N
L/Q	0.9872	likely_pathogenic	0.9923	pathogenic	-2.38	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/R	0.9852	likely_pathogenic	0.9922	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.524536823	None	None	N
L/S	0.9903	likely_pathogenic	0.9943	pathogenic	-3.259	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/T	0.9194	likely_pathogenic	0.944	pathogenic	-2.768	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/V	0.1531	likely_benign	0.1608	benign	-1.303	Destabilizing	0.999	D	0.573	neutral	N	0.43508384	None	None	N
L/W	0.9846	likely_pathogenic	0.9898	pathogenic	-1.833	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/Y	0.9903	likely_pathogenic	0.993	pathogenic	-1.689	Destabilizing	1.0	D	0.86	deleterious	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.