TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
N2AB	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
N2A	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
N2B	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
Novex-1	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
Novex-2	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980
Novex-3	60	403;404;405	chr2:178802255;178802254;178802253	chr2:179666982;179666981;179666980

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-1
• Domain position: 55
• Structural Position: 131
• Q(SASA): 0.7131
• 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
D/E	None	None	None	N	0.266	0.087	0.132336055621	gnomAD-4.0.0	2.05221E-06	None	None	None	0.089(TCAP)	N	None	0	0	None	0	0	None	0	0	2.69788E-06	0	0
D/N	rs35683768	0.317	0.308	N	0.443	0.18	0.12205267543	gnomAD-2.1.1	1.59E-05	None	None	None	-1.221(TCAP)	N	None	0	0	None	0	5.45E-05	None	0	None	0	2.64E-05	0
D/N	rs35683768	0.317	0.308	N	0.443	0.18	0.12205267543	gnomAD-3.1.2	6.57E-06	None	None	None	-1.221(TCAP)	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs35683768	0.317	0.308	N	0.443	0.18	0.12205267543	gnomAD-4.0.0	1.17724E-05	None	None	None	-1.221(TCAP)	N	None	4.00684E-05	0	None	0	2.22876E-05	None	0	0	1.01694E-05	2.19592E-05	1.60036E-05
D/V	rs754533155	0.36	0.281	D	0.526	0.356	0.451118754121	gnomAD-2.1.1	3.98E-06	None	None	None	0.313(TCAP)	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
D/V	rs754533155	0.36	0.281	D	0.526	0.356	0.451118754121	gnomAD-4.0.0	1.59052E-06	None	None	None	0.313(TCAP)	N	None	0	0	None	0	0	None	0	0	2.85649E-06	0	0
D/Y	rs35683768	0.073	0.992	N	0.511	0.344	None	gnomAD-2.1.1	1.46299E-02	None	None	None	0.118(TCAP)	N	None	6.98038E-02	1.13438E-02	None	4.82532E-03	9.04068E-03	None	1.36203E-02	None	1.73553E-02	6.38423E-03	1.16311E-02
D/Y	rs35683768	0.073	0.992	N	0.511	0.344	None	gnomAD-3.1.2	2.60441E-02	None	None	None	0.118(TCAP)	N	None	6.73579E-02	2.57165E-02	0	4.89631E-03	1.04126E-02	None	1.82007E-02	6.32911E-03	5.85053E-03	1.34799E-02	2.48566E-02
D/Y	rs35683768	0.073	0.992	N	0.511	0.344	None	1000 genomes	2.89537E-02	None	None	None	0.118(TCAP)	N	None	7.19E-02	2.02E-02	None	None	1.59E-02	8.9E-03	None	None	None	1.12E-02	None
D/Y	rs35683768	0.073	0.992	N	0.511	0.344	None	gnomAD-4.0.0	1.03547E-02	None	None	None	0.118(TCAP)	N	None	6.77265E-02	1.55599E-02	None	4.86355E-03	4.9271E-03	None	1.60565E-02	1.78277E-02	6.06439E-03	1.39886E-02	1.23184E-02

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
D/A	0.2778	likely_benign	0.2747	benign	-0.06	Destabilizing	0.081	N	0.421	neutral	N	0.479981992	None	-0.031(TCAP)	N
D/C	0.9101	likely_pathogenic	0.8802	pathogenic	-0.193	Destabilizing	0.847	D	0.586	neutral	None	None	None	-0.046(TCAP)	N
D/E	0.2253	likely_benign	0.2322	benign	-0.327	Destabilizing	None	N	0.266	neutral	N	0.449642912	None	0.089(TCAP)	N
D/F	0.8617	likely_pathogenic	0.8181	pathogenic	-0.044	Destabilizing	0.986	D	0.517	neutral	None	None	None	0.151(TCAP)	N
D/G	0.1865	likely_benign	0.1752	benign	-0.182	Destabilizing	0.114	N	0.487	neutral	N	0.431173787	None	-0.208(TCAP)	N
D/H	0.5179	ambiguous	0.4661	ambiguous	0.554	Stabilizing	0.942	D	0.453	neutral	N	0.508440468	None	0.805(TCAP)	N
D/I	0.8049	likely_pathogenic	0.7554	pathogenic	0.2	Stabilizing	0.857	D	0.531	neutral	None	None	None	0.473(TCAP)	N
D/K	0.5677	likely_pathogenic	0.5251	ambiguous	0.444	Stabilizing	0.297	N	0.441	neutral	None	None	None	0.42(TCAP)	N
D/L	0.6922	likely_pathogenic	0.6388	pathogenic	0.2	Stabilizing	0.747	D	0.527	neutral	None	None	None	0.473(TCAP)	N
D/M	0.8537	likely_pathogenic	0.8284	pathogenic	0.02	Stabilizing	0.963	D	0.543	neutral	None	None	None	0.958(TCAP)	N
D/N	0.1088	likely_benign	0.1043	benign	0.06	Stabilizing	0.308	N	0.443	neutral	N	0.45155417	None	-1.221(TCAP)	N
D/P	0.8703	likely_pathogenic	0.848	pathogenic	0.132	Stabilizing	0.106	N	0.455	neutral	None	None	None	0.313(TCAP)	N
D/Q	0.4496	ambiguous	0.4442	ambiguous	0.087	Stabilizing	0.356	N	0.485	neutral	None	None	None	-0.6(TCAP)	N
D/R	0.585	likely_pathogenic	0.5308	ambiguous	0.685	Stabilizing	0.597	D	0.451	neutral	None	None	None	0.252(TCAP)	N
D/S	0.1535	likely_benign	0.1505	benign	0.005	Stabilizing	0.021	N	0.297	neutral	None	None	None	-0.951(TCAP)	N
D/T	0.4595	ambiguous	0.4338	ambiguous	0.116	Stabilizing	0.05	N	0.439	neutral	None	None	None	-0.752(TCAP)	N
D/V	0.5969	likely_pathogenic	0.5396	ambiguous	0.132	Stabilizing	0.281	N	0.526	neutral	D	0.532394474	None	0.313(TCAP)	N
D/W	0.961	likely_pathogenic	0.9474	pathogenic	0.037	Stabilizing	0.986	D	0.615	neutral	None	None	None	-0.027(TCAP)	N
D/Y	0.5253	ambiguous	0.4045	ambiguous	0.188	Stabilizing	0.992	D	0.511	neutral	N	0.489528561	None	0.118(TCAP)	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.