TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7896	23911;23912;23913	chr2:178719806;178719805;178719804	chr2:179584533;179584532;179584531
N2AB	7579	22960;22961;22962	chr2:178719806;178719805;178719804	chr2:179584533;179584532;179584531
N2A	6652	20179;20180;20181	chr2:178719806;178719805;178719804	chr2:179584533;179584532;179584531
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-64
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4033
• 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
E/K	rs786205400	0.064	0.996	N	0.567	0.291	0.472344434578	gnomAD-2.1.1	2.03E-05	None	None	None	None	N	None	6.48E-05	2.92E-05	None	0	1.11719E-04	None	0	None	0	9.01E-06	0
E/K	rs786205400	0.064	0.996	N	0.567	0.291	0.472344434578	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs786205400	0.064	0.996	N	0.567	0.291	0.472344434578	gnomAD-4.0.0	9.92933E-06	None	None	None	None	N	None	1.3369E-05	1.67051E-05	None	0	4.46409E-05	None	0	1.64853E-04	9.33567E-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
E/A	0.1358	likely_benign	0.1222	benign	-0.142	Destabilizing	0.956	D	0.623	neutral	N	0.482921306	None	None	N
E/C	0.8394	likely_pathogenic	0.8051	pathogenic	-0.355	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.1749	likely_benign	0.1571	benign	-0.284	Destabilizing	0.121	N	0.23	neutral	N	0.517108657	None	None	N
E/F	0.6769	likely_pathogenic	0.6105	pathogenic	-0.096	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
E/G	0.1174	likely_benign	0.109	benign	-0.287	Destabilizing	0.978	D	0.613	neutral	D	0.53665721	None	None	N
E/H	0.4523	ambiguous	0.414	ambiguous	0.512	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
E/I	0.2908	likely_benign	0.2465	benign	0.195	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
E/K	0.1084	likely_benign	0.1035	benign	0.204	Stabilizing	0.996	D	0.567	neutral	N	0.499442829	None	None	N
E/L	0.3134	likely_benign	0.2642	benign	0.195	Stabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.3853	ambiguous	0.3315	benign	-0.095	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/N	0.2827	likely_benign	0.241	benign	-0.021	Destabilizing	0.983	D	0.595	neutral	None	None	None	None	N
E/P	0.5951	likely_pathogenic	0.5457	ambiguous	0.101	Stabilizing	0.998	D	0.733	prob.delet.	None	None	None	None	N
E/Q	0.1127	likely_benign	0.108	benign	0.002	Stabilizing	0.999	D	0.617	neutral	D	0.523245195	None	None	N
E/R	0.1984	likely_benign	0.188	benign	0.547	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	N
E/S	0.1804	likely_benign	0.1597	benign	-0.197	Destabilizing	0.693	D	0.298	neutral	None	None	None	None	N
E/T	0.215	likely_benign	0.1834	benign	-0.075	Destabilizing	0.967	D	0.659	neutral	None	None	None	None	N
E/V	0.1723	likely_benign	0.1475	benign	0.101	Stabilizing	0.997	D	0.679	prob.neutral	N	0.52032232	None	None	N
E/W	0.8848	likely_pathogenic	0.8521	pathogenic	-0.017	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/Y	0.5936	likely_pathogenic	0.5421	ambiguous	0.128	Stabilizing	0.999	D	0.71	prob.delet.	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.