TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30817	92674;92675;92676	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
N2AB	29176	87751;87752;87753	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
N2A	28249	84970;84971;84972	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
N2B	21752	65479;65480;65481	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
Novex-1	21877	65854;65855;65856	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
Novex-2	21944	66055;66056;66057	chr2:178549177;178549176;178549175	chr2:179413904;179413903;179413902
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: Fn3-112
• Domain position: 99
• Structural Position: 132
• Q(SASA): 1.2327
• 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	rs397517755	-0.065	0.007	N	0.345	0.036	0.104622674875	gnomAD-2.1.1	3.57E-05	None	None	None	None	N	None	0	2.83E-05	None	0	0	None	0	None	0	7.03E-05	0
E/D	rs397517755	-0.065	0.007	N	0.345	0.036	0.104622674875	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	8.82E-05	0	0
E/D	rs397517755	-0.065	0.007	N	0.345	0.036	0.104622674875	gnomAD-4.0.0	7.12671E-05	None	None	None	None	N	None	0	3.33489E-05	None	0	0	None	0	0	9.49299E-05	0	1.60133E-05
E/K	rs529196025	0.725	0.007	N	0.478	0.158	0.194818534648	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
E/K	rs529196025	0.725	0.007	N	0.478	0.158	0.194818534648	gnomAD-4.0.0	6.84219E-07	None	None	None	None	N	None	2.98775E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs529196025	0.49	0.79	N	0.539	0.094	0.210429274316	gnomAD-2.1.1	3.21E-05	None	None	None	None	N	None	0	8.5E-05	None	0	0	None	9.81E-05	None	0	7.81E-06	2.80899E-04
E/Q	rs529196025	0.49	0.79	N	0.539	0.094	0.210429274316	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	1.47E-05	2.07383E-04	0
E/Q	rs529196025	0.49	0.79	N	0.539	0.094	0.210429274316	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/Q	rs529196025	0.49	0.79	N	0.539	0.094	0.210429274316	gnomAD-4.0.0	1.17737E-05	None	None	None	None	N	None	0	1.16694E-04	None	0	0	None	0	0	4.23798E-06	5.48992E-05	3.20154E-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	0.2716	likely_benign	0.2071	benign	-0.318	Destabilizing	0.518	D	0.631	neutral	N	0.45333874	None	None	N
E/C	0.9061	likely_pathogenic	0.8764	pathogenic	-0.045	Destabilizing	0.996	D	0.823	deleterious	None	None	None	None	N
E/D	0.1512	likely_benign	0.1124	benign	-0.249	Destabilizing	0.007	N	0.345	neutral	N	0.375283388	None	None	N
E/F	0.8497	likely_pathogenic	0.7963	pathogenic	-0.265	Destabilizing	0.996	D	0.697	prob.delet.	None	None	None	None	N
E/G	0.296	likely_benign	0.2226	benign	-0.498	Destabilizing	0.682	D	0.471	neutral	N	0.484989799	None	None	N
E/H	0.6941	likely_pathogenic	0.6005	pathogenic	0.013	Stabilizing	0.987	D	0.522	neutral	None	None	None	None	N
E/I	0.5184	ambiguous	0.4552	ambiguous	0.116	Stabilizing	0.953	D	0.751	deleterious	None	None	None	None	N
E/K	0.3362	likely_benign	0.2578	benign	0.293	Stabilizing	0.007	N	0.478	neutral	N	0.458637721	None	None	N
E/L	0.4965	ambiguous	0.4255	ambiguous	0.116	Stabilizing	0.909	D	0.694	prob.delet.	None	None	None	None	N
E/M	0.5849	likely_pathogenic	0.5211	ambiguous	0.165	Stabilizing	0.996	D	0.7	prob.delet.	None	None	None	None	N
E/N	0.3764	ambiguous	0.2826	benign	0.066	Stabilizing	0.909	D	0.585	neutral	None	None	None	None	N
E/P	0.578	likely_pathogenic	0.4642	ambiguous	-0.009	Destabilizing	0.953	D	0.599	neutral	None	None	None	None	N
E/Q	0.2266	likely_benign	0.1795	benign	0.092	Stabilizing	0.79	D	0.539	neutral	N	0.498919101	None	None	N
E/R	0.4919	ambiguous	0.403	ambiguous	0.498	Stabilizing	0.833	D	0.587	neutral	None	None	None	None	N
E/S	0.3279	likely_benign	0.2614	benign	-0.117	Destabilizing	0.587	D	0.627	neutral	None	None	None	None	N
E/T	0.3785	ambiguous	0.3169	benign	0.027	Stabilizing	0.909	D	0.578	neutral	None	None	None	None	N
E/V	0.3183	likely_benign	0.2639	benign	-0.009	Destabilizing	0.883	D	0.654	prob.neutral	N	0.448660541	None	None	N
E/W	0.9529	likely_pathogenic	0.9292	pathogenic	-0.149	Destabilizing	0.996	D	0.839	deleterious	None	None	None	None	N
E/Y	0.7376	likely_pathogenic	0.65	pathogenic	-0.035	Destabilizing	0.984	D	0.669	prob.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.