TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8990	27193;27194;27195	chr2:178713166;178713165;178713164	chr2:179577893;179577892;179577891
N2AB	8673	26242;26243;26244	chr2:178713166;178713165;178713164	chr2:179577893;179577892;179577891
N2A	7746	23461;23462;23463	chr2:178713166;178713165;178713164	chr2:179577893;179577892;179577891
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-75
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.7111
• 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	None	None	None	N	0.116	0.09	0.186928172975	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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	0.0733	likely_benign	0.0746	benign	-0.205	Destabilizing	0.003	N	0.175	neutral	N	0.404702218	None	None	N
E/C	0.5385	ambiguous	0.6337	pathogenic	0.102	Stabilizing	0.497	N	0.233	neutral	None	None	None	None	N
E/D	0.0659	likely_benign	0.0823	benign	-0.237	Destabilizing	None	N	0.082	neutral	N	0.459691496	None	None	N
E/F	0.3891	ambiguous	0.4423	ambiguous	-0.227	Destabilizing	0.138	N	0.332	neutral	None	None	None	None	N
E/G	0.0731	likely_benign	0.0794	benign	-0.347	Destabilizing	None	N	0.121	neutral	N	0.487704817	None	None	N
E/H	0.213	likely_benign	0.2405	benign	0.102	Stabilizing	0.245	N	0.19	neutral	None	None	None	None	N
E/I	0.1542	likely_benign	0.1827	benign	0.12	Stabilizing	0.022	N	0.316	neutral	None	None	None	None	N
E/K	0.0775	likely_benign	0.0793	benign	0.586	Stabilizing	None	N	0.116	neutral	N	0.440796304	None	None	N
E/L	0.1812	likely_benign	0.2128	benign	0.12	Stabilizing	None	N	0.158	neutral	None	None	None	None	N
E/M	0.2405	likely_benign	0.2672	benign	0.166	Stabilizing	0.002	N	0.156	neutral	None	None	None	None	N
E/N	0.1018	likely_benign	0.1367	benign	0.292	Stabilizing	0.009	N	0.132	neutral	None	None	None	None	N
E/P	0.1662	likely_benign	0.1749	benign	0.031	Stabilizing	0.085	N	0.273	neutral	None	None	None	None	N
E/Q	0.0984	likely_benign	0.0999	benign	0.308	Stabilizing	0.001	N	0.214	neutral	N	0.470657851	None	None	N
E/R	0.1322	likely_benign	0.1298	benign	0.684	Stabilizing	0.022	N	0.128	neutral	None	None	None	None	N
E/S	0.0892	likely_benign	0.1012	benign	0.173	Stabilizing	0.009	N	0.142	neutral	None	None	None	None	N
E/T	0.112	likely_benign	0.1219	benign	0.297	Stabilizing	None	N	0.143	neutral	None	None	None	None	N
E/V	0.1029	likely_benign	0.117	benign	0.031	Stabilizing	0.007	N	0.177	neutral	N	0.460190142	None	None	N
E/W	0.5972	likely_pathogenic	0.6257	pathogenic	-0.138	Destabilizing	0.788	D	0.232	neutral	None	None	None	None	N
E/Y	0.2432	likely_benign	0.2948	benign	0.009	Stabilizing	0.497	N	0.309	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.