TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9262	28009;28010;28011	chr2:178712046;178712045;178712044	chr2:179576773;179576772;179576771
N2AB	8945	27058;27059;27060	chr2:178712046;178712045;178712044	chr2:179576773;179576772;179576771
N2A	8018	24277;24278;24279	chr2:178712046;178712045;178712044	chr2:179576773;179576772;179576771
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-78
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0522
• 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	rs897313799	None	0.999	D	0.655	0.596	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs897313799	None	0.999	D	0.655	0.596	None	gnomAD-4.0.0	6.57125E-06	None	None	None	None	N	None	2.41255E-05	0	None	0	0	None	0	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
L/A	0.8892	likely_pathogenic	0.926	pathogenic	-2.049	Highly Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
L/C	0.9124	likely_pathogenic	0.9417	pathogenic	-1.353	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-2.898	Highly Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9985	pathogenic	-2.583	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/F	0.6029	likely_pathogenic	0.7123	pathogenic	-1.291	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/G	0.9894	likely_pathogenic	0.9938	pathogenic	-2.62	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/H	0.9891	likely_pathogenic	0.9951	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/I	0.2096	likely_benign	0.2226	benign	-0.334	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
L/K	0.995	likely_pathogenic	0.9973	pathogenic	-1.525	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/M	0.2693	likely_benign	0.3347	benign	-0.597	Destabilizing	1.0	D	0.802	deleterious	D	0.542943107	None	None	N
L/N	0.9971	likely_pathogenic	0.9983	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
L/P	0.9978	likely_pathogenic	0.9988	pathogenic	-0.897	Destabilizing	1.0	D	0.939	deleterious	D	0.58248298	None	None	N
L/Q	0.9849	likely_pathogenic	0.9931	pathogenic	-1.855	Destabilizing	1.0	D	0.945	deleterious	D	0.58248298	None	None	N
L/R	0.9849	likely_pathogenic	0.9927	pathogenic	-1.873	Destabilizing	1.0	D	0.941	deleterious	D	0.57096209	None	None	N
L/S	0.9896	likely_pathogenic	0.995	pathogenic	-2.717	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/T	0.9619	likely_pathogenic	0.9762	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
L/V	0.2311	likely_benign	0.2748	benign	-0.897	Destabilizing	0.999	D	0.655	neutral	D	0.533966658	None	None	N
L/W	0.9614	likely_pathogenic	0.9841	pathogenic	-1.682	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
L/Y	0.9705	likely_pathogenic	0.9826	pathogenic	-1.415	Destabilizing	1.0	D	0.884	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.