TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18208	54847;54848;54849	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
N2AB	16567	49924;49925;49926	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
N2A	15640	47143;47144;47145	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
N2B	9143	27652;27653;27654	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
Novex-1	9268	28027;28028;28029	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
Novex-2	9335	28228;28229;28230	chr2:178604065;178604064;178604063	chr2:179468792;179468791;179468790
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: Fn3-20
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4099
• 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	rs575533984	-0.419	0.001	N	0.131	0.253	0.221734844693	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	0	1.65837E-04
E/K	rs575533984	-0.419	0.001	N	0.131	0.253	0.221734844693	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
E/K	rs575533984	-0.419	0.001	N	0.131	0.253	0.221734844693	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	rs575533984	-0.419	0.001	N	0.131	0.253	0.221734844693	gnomAD-4.0.0	6.20001E-06	None	None	None	None	N	None	0	1.66744E-05	None	0	0	None	0	0	1.6961E-06	7.6918E-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	0.1093	likely_benign	0.0907	benign	-0.7	Destabilizing	0.101	N	0.367	neutral	N	0.406561592	None	None	N
E/C	0.7862	likely_pathogenic	0.7642	pathogenic	-0.287	Destabilizing	0.951	D	0.528	neutral	None	None	None	None	N
E/D	0.152	likely_benign	0.1289	benign	-0.762	Destabilizing	0.312	N	0.255	neutral	N	0.427648941	None	None	N
E/F	0.7013	likely_pathogenic	0.6088	pathogenic	-0.427	Destabilizing	0.716	D	0.544	neutral	None	None	None	None	N
E/G	0.2148	likely_benign	0.1532	benign	-0.972	Destabilizing	0.523	D	0.467	neutral	N	0.404620152	None	None	N
E/H	0.5432	ambiguous	0.4408	ambiguous	-0.482	Destabilizing	0.94	D	0.383	neutral	None	None	None	None	N
E/I	0.2248	likely_benign	0.1875	benign	0.013	Stabilizing	0.11	N	0.496	neutral	None	None	None	None	N
E/K	0.2286	likely_benign	0.1646	benign	-0.222	Destabilizing	0.001	N	0.131	neutral	N	0.355498054	None	None	N
E/L	0.3222	likely_benign	0.2467	benign	0.013	Stabilizing	0.129	N	0.505	neutral	None	None	None	None	N
E/M	0.371	ambiguous	0.2982	benign	0.281	Stabilizing	0.716	D	0.525	neutral	None	None	None	None	N
E/N	0.3056	likely_benign	0.2442	benign	-0.563	Destabilizing	0.593	D	0.24	neutral	None	None	None	None	N
E/P	0.4479	ambiguous	0.4303	ambiguous	-0.204	Destabilizing	0.816	D	0.441	neutral	None	None	None	None	N
E/Q	0.1951	likely_benign	0.1487	benign	-0.509	Destabilizing	0.351	N	0.272	neutral	N	0.456374337	None	None	N
E/R	0.355	ambiguous	0.2637	benign	0.035	Stabilizing	0.264	N	0.212	neutral	None	None	None	None	N
E/S	0.2043	likely_benign	0.1595	benign	-0.783	Destabilizing	0.228	N	0.24	neutral	None	None	None	None	N
E/T	0.1961	likely_benign	0.1477	benign	-0.568	Destabilizing	0.228	N	0.376	neutral	None	None	None	None	N
E/V	0.1335	likely_benign	0.1125	benign	-0.204	Destabilizing	0.001	N	0.263	neutral	N	0.401731776	None	None	N
E/W	0.8872	likely_pathogenic	0.8342	pathogenic	-0.221	Destabilizing	0.983	D	0.552	neutral	None	None	None	None	N
E/Y	0.593	likely_pathogenic	0.5031	ambiguous	-0.186	Destabilizing	0.836	D	0.523	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.