TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5677	17254;17255;17256	chr2:178731846;178731845;178731844	chr2:179596573;179596572;179596571
N2AB	5360	16303;16304;16305	chr2:178731846;178731845;178731844	chr2:179596573;179596572;179596571
N2A	4433	13522;13523;13524	chr2:178731846;178731845;178731844	chr2:179596573;179596572;179596571
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-40
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1511
• Predicted PPI site: I

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/M	rs770682637	-0.412	0.984	N	0.623	0.317	0.602240183744	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
L/M	rs770682637	-0.412	0.984	N	0.623	0.317	0.602240183744	gnomAD-4.0.0	3.18263E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71706E-06	0	0
L/P	rs1269227302	-1.175	0.995	D	0.767	0.58	0.871642052151	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
L/P	rs1269227302	-1.175	0.995	D	0.767	0.58	0.871642052151	gnomAD-4.0.0	3.42106E-06	None	None	None	None	I	None	0	2.23624E-05	None	0	0	None	0	0	1.79898E-06	2.31863E-05	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	0.7278	likely_pathogenic	0.6391	pathogenic	-1.825	Destabilizing	0.702	D	0.562	neutral	None	None	None	None	I
L/C	0.7747	likely_pathogenic	0.7404	pathogenic	-0.986	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
L/D	0.9883	likely_pathogenic	0.9819	pathogenic	-1.744	Destabilizing	0.996	D	0.767	deleterious	None	None	None	None	I
L/E	0.9057	likely_pathogenic	0.8635	pathogenic	-1.496	Destabilizing	0.988	D	0.732	prob.delet.	None	None	None	None	I
L/F	0.3399	likely_benign	0.3133	benign	-1.084	Destabilizing	0.976	D	0.571	neutral	None	None	None	None	I
L/G	0.9332	likely_pathogenic	0.9023	pathogenic	-2.337	Highly Destabilizing	0.988	D	0.719	prob.delet.	None	None	None	None	I
L/H	0.7691	likely_pathogenic	0.7068	pathogenic	-1.772	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	I
L/I	0.0781	likely_benign	0.0764	benign	-0.346	Destabilizing	0.06	N	0.216	neutral	None	None	None	None	I
L/K	0.8576	likely_pathogenic	0.8007	pathogenic	-1.041	Destabilizing	0.988	D	0.695	prob.neutral	None	None	None	None	I
L/M	0.1982	likely_benign	0.1831	benign	-0.382	Destabilizing	0.984	D	0.623	neutral	N	0.494275428	None	None	I
L/N	0.919	likely_pathogenic	0.8791	pathogenic	-1.439	Destabilizing	0.996	D	0.769	deleterious	None	None	None	None	I
L/P	0.8799	likely_pathogenic	0.838	pathogenic	-0.821	Destabilizing	0.995	D	0.767	deleterious	D	0.531333312	None	None	I
L/Q	0.6463	likely_pathogenic	0.5629	ambiguous	-1.211	Destabilizing	0.995	D	0.726	prob.delet.	N	0.520230496	None	None	I
L/R	0.7731	likely_pathogenic	0.7061	pathogenic	-1.086	Destabilizing	0.984	D	0.725	prob.delet.	D	0.542854202	None	None	I
L/S	0.8574	likely_pathogenic	0.7929	pathogenic	-2.127	Highly Destabilizing	0.988	D	0.656	neutral	None	None	None	None	I
L/T	0.7019	likely_pathogenic	0.6085	pathogenic	-1.718	Destabilizing	0.919	D	0.589	neutral	None	None	None	None	I
L/V	0.1044	likely_benign	0.0959	benign	-0.821	Destabilizing	0.011	N	0.225	neutral	N	0.481769506	None	None	I
L/W	0.7016	likely_pathogenic	0.6566	pathogenic	-1.359	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
L/Y	0.7911	likely_pathogenic	0.745	pathogenic	-1.007	Destabilizing	0.988	D	0.703	prob.neutral	None	None	None	None	I

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.