TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26702	80329;80330;80331	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
N2AB	25061	75406;75407;75408	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
N2A	24134	72625;72626;72627	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
N2B	17637	53134;53135;53136	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
Novex-1	17762	53509;53510;53511	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
Novex-2	17829	53710;53711;53712	chr2:178566028;178566027;178566026	chr2:179430755;179430754;179430753
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: Fn3-82
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0929
• 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/V	rs746800300	-1.445	0.999	N	0.569	0.344	0.566919426312	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
L/V	rs746800300	-1.445	0.999	N	0.569	0.344	0.566919426312	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71919E-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	0.8898	likely_pathogenic	0.9084	pathogenic	-2.457	Highly Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
L/C	0.8614	likely_pathogenic	0.8936	pathogenic	-1.186	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/E	0.9978	likely_pathogenic	0.9975	pathogenic	-2.723	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/F	0.6448	likely_pathogenic	0.6542	pathogenic	-1.498	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
L/G	0.9922	likely_pathogenic	0.9925	pathogenic	-2.997	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.9938	likely_pathogenic	0.9927	pathogenic	-2.833	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/I	0.1033	likely_benign	0.1063	benign	-0.807	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
L/K	0.9968	likely_pathogenic	0.9961	pathogenic	-1.846	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/M	0.3413	ambiguous	0.3656	ambiguous	-0.87	Destabilizing	1.0	D	0.71	prob.delet.	N	0.512835939	None	None	N
L/N	0.9983	likely_pathogenic	0.9982	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/P	0.9926	likely_pathogenic	0.9916	pathogenic	-1.353	Destabilizing	1.0	D	0.92	deleterious	D	0.559186213	None	None	N
L/Q	0.9913	likely_pathogenic	0.99	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.914	deleterious	D	0.559186213	None	None	N
L/R	0.9907	likely_pathogenic	0.9885	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.559186213	None	None	N
L/S	0.9917	likely_pathogenic	0.9922	pathogenic	-2.963	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/T	0.9442	likely_pathogenic	0.9498	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/V	0.1236	likely_benign	0.1392	benign	-1.353	Destabilizing	0.999	D	0.569	neutral	N	0.510384967	None	None	N
L/W	0.9773	likely_pathogenic	0.9737	pathogenic	-1.736	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
L/Y	0.9832	likely_pathogenic	0.9834	pathogenic	-1.657	Destabilizing	1.0	D	0.821	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.