TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17636	53131;53132;53133	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
N2AB	15995	48208;48209;48210	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
N2A	15068	45427;45428;45429	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
N2B	8571	25936;25937;25938	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
Novex-1	8696	26311;26312;26313	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
Novex-2	8763	26512;26513;26514	chr2:178607881;178607880;178607879	chr2:179472608;179472607;179472606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-16
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4746
• 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/D	rs748175453	-0.417	0.999	N	0.6	0.287	0.40722173914	gnomAD-2.1.1	8.22E-05	None	None	None	None	N	None	0	0	None	0	1.18863E-03	None	0	None	0	0	0
E/D	rs748175453	-0.417	0.999	N	0.6	0.287	0.40722173914	gnomAD-3.1.2	4.61E-05	None	None	None	None	N	None	0	6.56E-05	0	0	1.16686E-03	None	0	0	0	0	0
E/D	rs748175453	-0.417	0.999	N	0.6	0.287	0.40722173914	gnomAD-4.0.0	1.98384E-05	None	None	None	None	N	None	0	1.66783E-05	None	0	6.70961E-04	None	0	0	0	0	1.60169E-05

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	0.2168	likely_benign	0.2096	benign	-0.232	Destabilizing	0.999	D	0.661	neutral	D	0.522596542	None	None	N
E/C	0.9319	likely_pathogenic	0.9299	pathogenic	0.055	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.398	ambiguous	0.3722	ambiguous	-0.32	Destabilizing	0.999	D	0.6	neutral	N	0.484334933	None	None	N
E/F	0.9481	likely_pathogenic	0.9398	pathogenic	-0.197	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/G	0.3413	ambiguous	0.327	benign	-0.4	Destabilizing	1.0	D	0.621	neutral	N	0.497919737	None	None	N
E/H	0.7781	likely_pathogenic	0.7739	pathogenic	0.12	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
E/I	0.6293	likely_pathogenic	0.6289	pathogenic	0.163	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/K	0.2581	likely_benign	0.2509	benign	0.553	Stabilizing	0.999	D	0.707	prob.neutral	N	0.471141748	None	None	N
E/L	0.7009	likely_pathogenic	0.6973	pathogenic	0.163	Stabilizing	1.0	D	0.646	neutral	None	None	None	None	N
E/M	0.7014	likely_pathogenic	0.6909	pathogenic	0.184	Stabilizing	1.0	D	0.621	neutral	None	None	None	None	N
E/N	0.5662	likely_pathogenic	0.5453	ambiguous	0.215	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
E/P	0.5104	ambiguous	0.5077	ambiguous	0.051	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/Q	0.2017	likely_benign	0.2024	benign	0.23	Stabilizing	1.0	D	0.682	prob.neutral	N	0.471395238	None	None	N
E/R	0.4466	ambiguous	0.4406	ambiguous	0.705	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/S	0.3974	ambiguous	0.381	ambiguous	0.09	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/T	0.3981	ambiguous	0.394	ambiguous	0.23	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/V	0.3759	ambiguous	0.3726	ambiguous	0.051	Stabilizing	1.0	D	0.625	neutral	N	0.477093231	None	None	N
E/W	0.9788	likely_pathogenic	0.9774	pathogenic	-0.081	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/Y	0.8993	likely_pathogenic	0.8868	pathogenic	0.05	Stabilizing	1.0	D	0.617	neutral	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.