TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19984	60175;60176;60177	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
N2AB	18343	55252;55253;55254	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
N2A	17416	52471;52472;52473	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
N2B	10919	32980;32981;32982	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
Novex-1	11044	33355;33356;33357	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
Novex-2	11111	33556;33557;33558	chr2:178591869;178591868;178591867	chr2:179456596;179456595;179456594
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: Fn3-33
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1963
• 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/M	None	None	1.0	N	0.799	0.361	0.551344072312	gnomAD-4.0.0	6.85192E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.999E-07	0	0
L/P	None	None	1.0	N	0.893	0.562	0.804142074079	gnomAD-4.0.0	1.59401E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4379E-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	0.97	likely_pathogenic	0.973	pathogenic	-2.444	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	I
L/C	0.9104	likely_pathogenic	0.9225	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.422	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
L/E	0.9984	likely_pathogenic	0.9988	pathogenic	-3.197	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
L/F	0.8432	likely_pathogenic	0.9133	pathogenic	-1.227	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	I
L/G	0.9946	likely_pathogenic	0.9958	pathogenic	-2.957	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
L/H	0.9933	likely_pathogenic	0.9965	pathogenic	-2.619	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
L/I	0.2846	likely_benign	0.2969	benign	-0.943	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
L/K	0.9942	likely_pathogenic	0.9962	pathogenic	-1.929	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
L/M	0.5608	ambiguous	0.6216	pathogenic	-1.182	Destabilizing	1.0	D	0.799	deleterious	N	0.50579482	None	None	I
L/N	0.9959	likely_pathogenic	0.9971	pathogenic	-2.381	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	I
L/P	0.9898	likely_pathogenic	0.9924	pathogenic	-1.429	Destabilizing	1.0	D	0.893	deleterious	N	0.468466561	None	None	I
L/Q	0.9914	likely_pathogenic	0.9944	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.889	deleterious	N	0.513392144	None	None	I
L/R	0.9856	likely_pathogenic	0.9906	pathogenic	-1.742	Destabilizing	1.0	D	0.892	deleterious	D	0.524913033	None	None	I
L/S	0.9957	likely_pathogenic	0.9967	pathogenic	-2.91	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
L/T	0.9571	likely_pathogenic	0.9592	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
L/V	0.2814	likely_benign	0.2481	benign	-1.429	Destabilizing	0.999	D	0.675	prob.neutral	N	0.491145846	None	None	I
L/W	0.9902	likely_pathogenic	0.9953	pathogenic	-1.797	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
L/Y	0.9908	likely_pathogenic	0.9955	pathogenic	-1.559	Destabilizing	1.0	D	0.851	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.