TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20903	62932;62933;62934	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
N2AB	19262	58009;58010;58011	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
N2A	18335	55228;55229;55230	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
N2B	11838	35737;35738;35739	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
Novex-1	11963	36112;36113;36114	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
Novex-2	12030	36313;36314;36315	chr2:178589018;178589017;178589016	chr2:179453745;179453744;179453743
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-39
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2434
• 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
K/E	None	None	0.999	N	0.73	0.485	0.402755899245	gnomAD-4.0.0	1.5984E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.95802E-05	0	0	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
K/A	0.9854	likely_pathogenic	0.9895	pathogenic	-1.487	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
K/C	0.9711	likely_pathogenic	0.9809	pathogenic	-1.355	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/D	0.9973	likely_pathogenic	0.9983	pathogenic	-1.791	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
K/E	0.986	likely_pathogenic	0.9917	pathogenic	-1.454	Destabilizing	0.999	D	0.73	prob.delet.	N	0.509236363	None	None	N
K/F	0.9905	likely_pathogenic	0.9948	pathogenic	-0.868	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
K/G	0.9888	likely_pathogenic	0.9924	pathogenic	-1.982	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/H	0.8902	likely_pathogenic	0.9258	pathogenic	-1.638	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/I	0.9451	likely_pathogenic	0.964	pathogenic	-0.061	Destabilizing	1.0	D	0.901	deleterious	N	0.475279124	None	None	N
K/L	0.9446	likely_pathogenic	0.9601	pathogenic	-0.061	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
K/M	0.8965	likely_pathogenic	0.9249	pathogenic	-0.401	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/N	0.9914	likely_pathogenic	0.9951	pathogenic	-1.583	Destabilizing	1.0	D	0.829	deleterious	N	0.520757252	None	None	N
K/P	0.9983	likely_pathogenic	0.9989	pathogenic	-0.519	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
K/Q	0.8806	likely_pathogenic	0.923	pathogenic	-1.18	Destabilizing	1.0	D	0.832	deleterious	N	0.481257059	None	None	N
K/R	0.2184	likely_benign	0.2558	benign	-0.466	Destabilizing	0.999	D	0.725	prob.delet.	N	0.49625809	None	None	N
K/S	0.993	likely_pathogenic	0.9959	pathogenic	-2.186	Highly Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
K/T	0.9564	likely_pathogenic	0.9729	pathogenic	-1.565	Destabilizing	1.0	D	0.827	deleterious	N	0.507968915	None	None	N
K/V	0.9336	likely_pathogenic	0.9571	pathogenic	-0.519	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
K/W	0.9872	likely_pathogenic	0.9936	pathogenic	-0.825	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
K/Y	0.9558	likely_pathogenic	0.9758	pathogenic	-0.498	Destabilizing	1.0	D	0.891	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.