TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14298	43117;43118;43119	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
N2AB	12657	38194;38195;38196	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
N2A	11730	35413;35414;35415	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
N2B	5233	15922;15923;15924	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
Novex-1	5358	16297;16298;16299	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
Novex-2	5425	16498;16499;16500	chr2:178633467;178633466;178633465	chr2:179498194;179498193;179498192
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-93
• Domain position: 68
• Structural Position: 153
• Q(SASA): 0.3797
• 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	rs778634417	-0.389	0.198	D	0.499	0.238	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	6.46E-05	0	None	0	1.12183E-04	None	0	None	0	8.88E-06	0
E/K	rs778634417	-0.389	0.198	D	0.499	0.238	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	1.93274E-04	None	0	0	1.47E-05	0	0
E/K	rs778634417	-0.389	0.198	D	0.499	0.238	None	gnomAD-4.0.0	1.05379E-05	None	None	None	None	N	None	2.67073E-05	0	None	0	6.70391E-05	None	0	0	9.32524E-06	0	1.60205E-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	0.1426	likely_benign	0.1275	benign	-0.855	Destabilizing	0.042	N	0.49	neutral	N	0.504769058	None	None	N
E/C	0.7794	likely_pathogenic	0.7608	pathogenic	-0.415	Destabilizing	0.958	D	0.592	neutral	None	None	None	None	N
E/D	0.1078	likely_benign	0.1015	benign	-1.25	Destabilizing	0.001	N	0.174	neutral	N	0.51273392	None	None	N
E/F	0.5732	likely_pathogenic	0.5397	ambiguous	-0.555	Destabilizing	0.497	N	0.605	neutral	None	None	None	None	N
E/G	0.2103	likely_benign	0.165	benign	-1.208	Destabilizing	0.096	N	0.535	neutral	D	0.717472022	None	None	N
E/H	0.4143	ambiguous	0.3774	ambiguous	-0.901	Destabilizing	0.667	D	0.574	neutral	None	None	None	None	N
E/I	0.197	likely_benign	0.1773	benign	0.102	Stabilizing	0.124	N	0.54	neutral	None	None	None	None	N
E/K	0.1823	likely_benign	0.1249	benign	-0.645	Destabilizing	0.198	N	0.499	neutral	D	0.529246298	None	None	N
E/L	0.279	likely_benign	0.2647	benign	0.102	Stabilizing	0.001	N	0.409	neutral	None	None	None	None	N
E/M	0.3307	likely_benign	0.2946	benign	0.631	Stabilizing	0.497	N	0.588	neutral	None	None	None	None	N
E/N	0.1447	likely_benign	0.1406	benign	-1.052	Destabilizing	0.001	N	0.291	neutral	None	None	None	None	N
E/P	0.548	ambiguous	0.6041	pathogenic	-0.195	Destabilizing	0.667	D	0.61	neutral	None	None	None	None	N
E/Q	0.148	likely_benign	0.1272	benign	-0.934	Destabilizing	0.021	N	0.176	neutral	N	0.505261399	None	None	N
E/R	0.3007	likely_benign	0.2369	benign	-0.466	Destabilizing	0.22	N	0.522	neutral	None	None	None	None	N
E/S	0.1586	likely_benign	0.1456	benign	-1.363	Destabilizing	0.055	N	0.499	neutral	None	None	None	None	N
E/T	0.1499	likely_benign	0.1371	benign	-1.071	Destabilizing	0.22	N	0.536	neutral	None	None	None	None	N
E/V	0.137	likely_benign	0.1269	benign	-0.195	Destabilizing	0.001	N	0.405	neutral	N	0.501537122	None	None	N
E/W	0.8436	likely_pathogenic	0.8024	pathogenic	-0.392	Destabilizing	0.958	D	0.603	neutral	None	None	None	None	N
E/Y	0.5121	ambiguous	0.4626	ambiguous	-0.321	Destabilizing	0.859	D	0.605	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.