TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31208	93847;93848;93849	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
N2AB	29567	88924;88925;88926	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
N2A	28640	86143;86144;86145	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
N2B	22143	66652;66653;66654	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
Novex-1	22268	67027;67028;67029	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
Novex-2	22335	67228;67229;67230	chr2:178548004;178548003;178548002	chr2:179412731;179412730;179412729
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: Fn3-115
• Domain position: 96
• Structural Position: 132
• Q(SASA): 0.9272
• 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	None	None	0.018	N	0.337	0.094	0.201204373187	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
E/K	rs765216493	0.746	0.856	N	0.666	0.332	0.318828661733	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs765216493	0.746	0.856	N	0.666	0.332	0.318828661733	gnomAD-4.0.0	1.59142E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
E/A	0.5395	ambiguous	0.6315	pathogenic	-0.322	Destabilizing	0.856	D	0.713	prob.delet.	N	0.490900703	None	None	N
E/C	0.9781	likely_pathogenic	0.9862	pathogenic	-0.075	Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
E/D	0.2173	likely_benign	0.2609	benign	-0.313	Destabilizing	0.018	N	0.337	neutral	N	0.452555746	None	None	N
E/F	0.9767	likely_pathogenic	0.9873	pathogenic	-0.222	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	N
E/G	0.6326	likely_pathogenic	0.7155	pathogenic	-0.498	Destabilizing	0.954	D	0.626	neutral	D	0.531651248	None	None	N
E/H	0.9239	likely_pathogenic	0.955	pathogenic	0.097	Stabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
E/I	0.8588	likely_pathogenic	0.9024	pathogenic	0.102	Stabilizing	0.982	D	0.818	deleterious	None	None	None	None	N
E/K	0.7582	likely_pathogenic	0.8233	pathogenic	0.378	Stabilizing	0.856	D	0.666	prob.neutral	N	0.488487032	None	None	N
E/L	0.8572	likely_pathogenic	0.9044	pathogenic	0.102	Stabilizing	0.982	D	0.785	deleterious	None	None	None	None	N
E/M	0.8591	likely_pathogenic	0.9031	pathogenic	0.124	Stabilizing	0.998	D	0.852	deleterious	None	None	None	None	N
E/N	0.6559	likely_pathogenic	0.7399	pathogenic	0.045	Stabilizing	0.932	D	0.745	deleterious	None	None	None	None	N
E/P	0.843	likely_pathogenic	0.8723	pathogenic	-0.02	Destabilizing	0.982	D	0.781	deleterious	None	None	None	None	N
E/Q	0.5102	ambiguous	0.5988	pathogenic	0.077	Stabilizing	0.954	D	0.662	prob.neutral	N	0.48326002	None	None	N
E/R	0.8706	likely_pathogenic	0.9093	pathogenic	0.58	Stabilizing	0.982	D	0.777	deleterious	None	None	None	None	N
E/S	0.6293	likely_pathogenic	0.7301	pathogenic	-0.098	Destabilizing	0.887	D	0.69	prob.delet.	None	None	None	None	N
E/T	0.7172	likely_pathogenic	0.8125	pathogenic	0.05	Stabilizing	0.965	D	0.76	deleterious	None	None	None	None	N
E/V	0.7023	likely_pathogenic	0.77	pathogenic	-0.02	Destabilizing	0.977	D	0.778	deleterious	N	0.491021928	None	None	N
E/W	0.9918	likely_pathogenic	0.9946	pathogenic	-0.083	Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
E/Y	0.9432	likely_pathogenic	0.9632	pathogenic	0.019	Stabilizing	0.998	D	0.818	deleterious	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.