TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26995	81208;81209;81210	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
N2AB	25354	76285;76286;76287	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
N2A	24427	73504;73505;73506	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
N2B	17930	54013;54014;54015	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
Novex-1	18055	54388;54389;54390	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
Novex-2	18122	54589;54590;54591	chr2:178565149;178565148;178565147	chr2:179429876;179429875;179429874
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: Fn3-84
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.5523
• 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	rs397517719	-0.368	0.007	N	0.242	0.178	None	gnomAD-2.1.1	2.25553E-04	None	None	None	None	N	None	0	0	None	0	0	None	1.50721E-03	None	0	1.33285E-04	0
E/K	rs397517719	-0.368	0.007	N	0.242	0.178	None	gnomAD-3.1.2	1.31513E-04	None	None	None	None	N	None	2.41E-05	6.56E-05	0	0	0	None	0	0	2.05858E-04	8.285E-04	0
E/K	rs397517719	-0.368	0.007	N	0.242	0.178	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs397517719	-0.368	0.007	N	0.242	0.178	None	gnomAD-4.0.0	1.98983E-04	None	None	None	None	N	None	1.33394E-05	1.66828E-05	None	0	0	None	3.12607E-05	0	1.44974E-04	1.51688E-03	1.28082E-04

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	0.1377	likely_benign	0.1238	benign	-0.947	Destabilizing	0.684	D	0.559	neutral	N	0.508939386	None	None	N
E/C	0.774	likely_pathogenic	0.7365	pathogenic	-0.486	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
E/D	0.0848	likely_benign	0.074	benign	-1.04	Destabilizing	0.003	N	0.205	neutral	N	0.452854029	None	None	N
E/F	0.6854	likely_pathogenic	0.6266	pathogenic	-0.445	Destabilizing	0.984	D	0.625	neutral	None	None	None	None	N
E/G	0.1327	likely_benign	0.1216	benign	-1.291	Destabilizing	0.684	D	0.598	neutral	N	0.469726624	None	None	N
E/H	0.4134	ambiguous	0.3897	ambiguous	-0.642	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
E/I	0.3532	ambiguous	0.3065	benign	-0.011	Destabilizing	0.953	D	0.639	neutral	None	None	None	None	N
E/K	0.1684	likely_benign	0.1602	benign	-0.641	Destabilizing	0.007	N	0.242	neutral	N	0.476864253	None	None	N
E/L	0.2895	likely_benign	0.2434	benign	-0.011	Destabilizing	0.742	D	0.645	neutral	None	None	None	None	N
E/M	0.3848	ambiguous	0.3397	benign	0.412	Stabilizing	0.987	D	0.615	neutral	None	None	None	None	N
E/N	0.1368	likely_benign	0.1193	benign	-1.073	Destabilizing	0.59	D	0.547	neutral	None	None	None	None	N
E/P	0.782	likely_pathogenic	0.7313	pathogenic	-0.302	Destabilizing	0.953	D	0.636	neutral	None	None	None	None	N
E/Q	0.129	likely_benign	0.1197	benign	-0.959	Destabilizing	0.028	N	0.327	neutral	N	0.458241206	None	None	N
E/R	0.2983	likely_benign	0.2949	benign	-0.326	Destabilizing	0.59	D	0.559	neutral	None	None	None	None	N
E/S	0.1535	likely_benign	0.1357	benign	-1.368	Destabilizing	0.742	D	0.543	neutral	None	None	None	None	N
E/T	0.2247	likely_benign	0.1956	benign	-1.088	Destabilizing	0.742	D	0.587	neutral	None	None	None	None	N
E/V	0.2228	likely_benign	0.1942	benign	-0.302	Destabilizing	0.884	D	0.649	neutral	N	0.474246075	None	None	N
E/W	0.8983	likely_pathogenic	0.8796	pathogenic	-0.185	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
E/Y	0.5209	ambiguous	0.4682	ambiguous	-0.199	Destabilizing	0.984	D	0.631	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.