TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30671	92236;92237;92238	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
N2AB	29030	87313;87314;87315	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
N2A	28103	84532;84533;84534	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
N2B	21606	65041;65042;65043	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
Novex-1	21731	65416;65417;65418	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
Novex-2	21798	65617;65618;65619	chr2:178549711;178549710;178549709	chr2:179414438;179414437;179414436
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: Fn3-111
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.2103
• Predicted PPI site: I

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	None	None	0.012	N	0.117	0.049	0.0482279557977	gnomAD-4.0.0	6.84238E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99497E-07	0	0
E/K	None	None	0.801	N	0.365	0.207	0.28297238246	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	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	0.1499	likely_benign	0.1559	benign	-0.265	Destabilizing	0.454	N	0.423	neutral	N	0.424512635	None	None	I
E/C	0.808	likely_pathogenic	0.8187	pathogenic	-0.133	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	I
E/D	0.172	likely_benign	0.1957	benign	-1.154	Destabilizing	0.012	N	0.117	neutral	N	0.430283814	None	None	I
E/F	0.8738	likely_pathogenic	0.9053	pathogenic	0.594	Stabilizing	0.991	D	0.565	neutral	None	None	None	None	I
E/G	0.2424	likely_benign	0.2785	benign	-0.713	Destabilizing	0.625	D	0.422	neutral	N	0.447658853	None	None	I
E/H	0.5381	ambiguous	0.5832	pathogenic	0.347	Stabilizing	0.974	D	0.463	neutral	None	None	None	None	I
E/I	0.607	likely_pathogenic	0.6616	pathogenic	0.973	Stabilizing	0.949	D	0.563	neutral	None	None	None	None	I
E/K	0.2248	likely_benign	0.2738	benign	-0.273	Destabilizing	0.801	D	0.365	neutral	N	0.49233235	None	None	I
E/L	0.5943	likely_pathogenic	0.6404	pathogenic	0.973	Stabilizing	0.842	D	0.484	neutral	None	None	None	None	I
E/M	0.5835	likely_pathogenic	0.6152	pathogenic	1.339	Stabilizing	0.998	D	0.513	neutral	None	None	None	None	I
E/N	0.3356	likely_benign	0.3816	ambiguous	-1.039	Destabilizing	0.067	N	0.148	neutral	None	None	None	None	I
E/P	0.9615	likely_pathogenic	0.977	pathogenic	0.584	Stabilizing	0.974	D	0.529	neutral	None	None	None	None	I
E/Q	0.1781	likely_benign	0.1923	benign	-0.767	Destabilizing	0.891	D	0.402	neutral	N	0.517017364	None	None	I
E/R	0.3634	ambiguous	0.4212	ambiguous	-0.023	Destabilizing	0.915	D	0.424	neutral	None	None	None	None	I
E/S	0.193	likely_benign	0.2053	benign	-1.352	Destabilizing	0.172	N	0.125	neutral	None	None	None	None	I
E/T	0.2096	likely_benign	0.2161	benign	-0.954	Destabilizing	0.029	N	0.193	neutral	None	None	None	None	I
E/V	0.3391	likely_benign	0.3728	ambiguous	0.584	Stabilizing	0.801	D	0.462	neutral	N	0.491140272	None	None	I
E/W	0.9527	likely_pathogenic	0.9701	pathogenic	0.796	Stabilizing	0.998	D	0.599	neutral	None	None	None	None	I
E/Y	0.773	likely_pathogenic	0.8245	pathogenic	0.874	Stabilizing	0.991	D	0.542	neutral	None	None	None	None	I

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.