TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3276	10051;10052;10053	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
N2AB	3276	10051;10052;10053	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
N2A	3276	10051;10052;10053	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
N2B	3230	9913;9914;9915	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
Novex-1	3230	9913;9914;9915	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
Novex-2	3230	9913;9914;9915	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414
Novex-3	3276	10051;10052;10053	chr2:178764689;178764688;178764687	chr2:179629416;179629415;179629414

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-23
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.7926
• 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/G	rs377049518	-0.039	0.193	N	0.391	0.203	None	gnomAD-2.1.1	1.77E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.88E-05	0
E/G	rs377049518	-0.039	0.193	N	0.391	0.203	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	5.88E-05	0	0
E/G	rs377049518	-0.039	0.193	N	0.391	0.203	None	gnomAD-4.0.0	8.85982E-05	None	None	None	None	N	None	2.6693E-05	0	None	0	0	None	0	0	1.16948E-04	0	4.80092E-05
E/K	rs929694215	None	0.193	N	0.335	0.354	0.276065633971	gnomAD-4.0.0	3.18103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85654E-06	1.43275E-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	0.1951	likely_benign	0.2572	benign	-0.319	Destabilizing	0.09	N	0.36	neutral	N	0.48973954	None	None	N
E/C	0.909	likely_pathogenic	0.9595	pathogenic	-0.312	Destabilizing	0.981	D	0.441	neutral	None	None	None	None	N
E/D	0.1025	likely_benign	0.1344	benign	-0.32	Destabilizing	0.001	N	0.153	neutral	N	0.426654932	None	None	N
E/F	0.8781	likely_pathogenic	0.9458	pathogenic	-0.099	Destabilizing	0.932	D	0.429	neutral	None	None	None	None	N
E/G	0.0904	likely_benign	0.1149	benign	-0.499	Destabilizing	0.193	N	0.391	neutral	N	0.405104235	None	None	N
E/H	0.5476	ambiguous	0.7029	pathogenic	0.399	Stabilizing	0.818	D	0.34	neutral	None	None	None	None	N
E/I	0.7179	likely_pathogenic	0.8458	pathogenic	0.121	Stabilizing	0.818	D	0.453	neutral	None	None	None	None	N
E/K	0.1666	likely_benign	0.2423	benign	0.257	Stabilizing	0.193	N	0.335	neutral	N	0.473220113	None	None	N
E/L	0.6143	likely_pathogenic	0.7534	pathogenic	0.121	Stabilizing	0.388	N	0.483	neutral	None	None	None	None	N
E/M	0.6208	likely_pathogenic	0.7571	pathogenic	-0.011	Destabilizing	0.981	D	0.41	neutral	None	None	None	None	N
E/N	0.1804	likely_benign	0.252	benign	-0.163	Destabilizing	0.241	N	0.346	neutral	None	None	None	None	N
E/P	0.8296	likely_pathogenic	0.9167	pathogenic	-0.006	Destabilizing	0.818	D	0.415	neutral	None	None	None	None	N
E/Q	0.1456	likely_benign	0.19	benign	-0.106	Destabilizing	0.018	N	0.21	neutral	N	0.500555206	None	None	N
E/R	0.3012	likely_benign	0.4346	ambiguous	0.59	Stabilizing	0.388	N	0.371	neutral	None	None	None	None	N
E/S	0.1827	likely_benign	0.2375	benign	-0.306	Destabilizing	0.004	N	0.135	neutral	None	None	None	None	N
E/T	0.3093	likely_benign	0.4116	ambiguous	-0.147	Destabilizing	0.241	N	0.417	neutral	None	None	None	None	N
E/V	0.5079	ambiguous	0.6566	pathogenic	-0.006	Destabilizing	0.324	N	0.475	neutral	D	0.595341902	None	None	N
E/W	0.9382	likely_pathogenic	0.9768	pathogenic	0.066	Stabilizing	0.981	D	0.521	neutral	None	None	None	None	N
E/Y	0.7277	likely_pathogenic	0.8631	pathogenic	0.144	Stabilizing	0.932	D	0.411	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.