TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23499	70720;70721;70722	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
N2AB	21858	65797;65798;65799	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
N2A	20931	63016;63017;63018	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
N2B	14434	43525;43526;43527	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
Novex-1	14559	43900;43901;43902	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
Novex-2	14626	44101;44102;44103	chr2:178575637;178575636;178575635	chr2:179440364;179440363;179440362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-58
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.1201
• 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/F	rs75626265	-2.286	1.0	D	0.855	0.645	0.850636553644	gnomAD-4.0.0	6.37414E-05	None	None	None	None	N	None	5.65803E-05	0	None	0	3.06407E-04	None	4.93246E-04	0	0	0	6.06428E-05
L/S	None	None	1.0	D	0.826	0.768	0.901367598863	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9638	likely_pathogenic	0.9721	pathogenic	-2.432	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/C	0.9372	likely_pathogenic	0.9554	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/D	0.9992	likely_pathogenic	0.9994	pathogenic	-1.722	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/E	0.9968	likely_pathogenic	0.9976	pathogenic	-1.637	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
L/F	0.7595	likely_pathogenic	0.7924	pathogenic	-1.898	Destabilizing	1.0	D	0.855	deleterious	D	0.649885539	None	None	N
L/G	0.9923	likely_pathogenic	0.9933	pathogenic	-2.839	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/H	0.9906	likely_pathogenic	0.9921	pathogenic	-1.958	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
L/I	0.2574	likely_benign	0.3279	benign	-1.326	Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
L/K	0.9931	likely_pathogenic	0.994	pathogenic	-1.721	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
L/M	0.4407	ambiguous	0.4863	ambiguous	-1.279	Destabilizing	1.0	D	0.837	deleterious	D	0.640366789	None	None	N
L/N	0.9924	likely_pathogenic	0.9939	pathogenic	-1.74	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/P	0.992	likely_pathogenic	0.9937	pathogenic	-1.669	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/Q	0.9842	likely_pathogenic	0.9875	pathogenic	-1.839	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/R	0.9864	likely_pathogenic	0.9878	pathogenic	-1.161	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/S	0.993	likely_pathogenic	0.995	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.826	deleterious	D	0.682963643	None	None	N
L/T	0.9592	likely_pathogenic	0.9697	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/V	0.3501	ambiguous	0.4374	ambiguous	-1.669	Destabilizing	0.996	D	0.837	deleterious	D	0.614626873	None	None	N
L/W	0.9792	likely_pathogenic	0.9833	pathogenic	-1.912	Destabilizing	1.0	D	0.755	deleterious	D	0.682963643	None	None	N
L/Y	0.9814	likely_pathogenic	0.9853	pathogenic	-1.71	Destabilizing	0.999	D	0.813	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.