TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17690	53293;53294;53295	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
N2AB	16049	48370;48371;48372	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
N2A	15122	45589;45590;45591	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
N2B	8625	26098;26099;26100	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
Novex-1	8750	26473;26474;26475	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
Novex-2	8817	26674;26675;26676	chr2:178607620;178607619;178607618	chr2:179472347;179472346;179472345
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-113
• Domain position: 14
• Structural Position: 28
• Q(SASA): 0.1491
• 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/P	rs370469461	-1.445	0.999	N	0.871	0.597	0.805114648059	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	6.49E-05	2.9E-05	None	0	0	None	0	None	0	0	0
L/P	rs370469461	-1.445	0.999	N	0.871	0.597	0.805114648059	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20691E-04	0	0	0	0	None	0	0	0	0	0
L/P	rs370469461	-1.445	0.999	N	0.871	0.597	0.805114648059	gnomAD-4.0.0	7.69387E-06	None	None	None	None	N	None	8.46339E-05	1.69601E-05	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	0.9064	likely_pathogenic	0.9256	pathogenic	-2.718	Highly Destabilizing	0.983	D	0.679	prob.neutral	None	None	None	None	N
L/C	0.892	likely_pathogenic	0.8998	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9995	pathogenic	-3.168	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/E	0.9942	likely_pathogenic	0.9968	pathogenic	-2.906	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
L/F	0.5398	ambiguous	0.6137	pathogenic	-1.671	Destabilizing	0.993	D	0.779	deleterious	N	0.488534323	None	None	N
L/G	0.9911	likely_pathogenic	0.9939	pathogenic	-3.296	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/H	0.9839	likely_pathogenic	0.9907	pathogenic	-2.71	Highly Destabilizing	1.0	D	0.854	deleterious	N	0.477523033	None	None	N
L/I	0.0972	likely_benign	0.1195	benign	-1.028	Destabilizing	0.117	N	0.278	neutral	N	0.410033467	None	None	N
L/K	0.9869	likely_pathogenic	0.9928	pathogenic	-2.352	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
L/M	0.3084	likely_benign	0.3338	benign	-0.952	Destabilizing	0.995	D	0.759	deleterious	None	None	None	None	N
L/N	0.9937	likely_pathogenic	0.9965	pathogenic	-2.816	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/P	0.9883	likely_pathogenic	0.993	pathogenic	-1.575	Destabilizing	0.999	D	0.871	deleterious	N	0.495627288	None	None	N
L/Q	0.9782	likely_pathogenic	0.9865	pathogenic	-2.618	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/R	0.9768	likely_pathogenic	0.9866	pathogenic	-2.091	Highly Destabilizing	0.999	D	0.859	deleterious	N	0.495373799	None	None	N
L/S	0.9887	likely_pathogenic	0.9929	pathogenic	-3.504	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
L/T	0.9515	likely_pathogenic	0.9656	pathogenic	-3.078	Highly Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
L/V	0.1569	likely_benign	0.1834	benign	-1.575	Destabilizing	0.898	D	0.536	neutral	N	0.414204349	None	None	N
L/W	0.9368	likely_pathogenic	0.9587	pathogenic	-2.055	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/Y	0.9551	likely_pathogenic	0.9684	pathogenic	-1.773	Destabilizing	0.999	D	0.843	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.