TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21221	63886;63887;63888	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
N2AB	19580	58963;58964;58965	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
N2A	18653	56182;56183;56184	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
N2B	12156	36691;36692;36693	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
Novex-1	12281	37066;37067;37068	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
Novex-2	12348	37267;37268;37269	chr2:178587648;178587647;178587646	chr2:179452375;179452374;179452373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-123
• Domain position: 45
• Structural Position: 122
• Q(SASA): 0.5809
• 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
Q/H	None	None	0.015	N	0.131	0.128	0.101711395817	gnomAD-4.0.0	1.59339E-06	None	None	None	None	I	None	0	2.28906E-05	None	0	0	None	0	0	0	0	0
Q/K	rs2049322891	None	0.826	N	0.376	0.246	0.219573609325	gnomAD-4.0.0	1.5935E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86092E-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
Q/A	0.2205	likely_benign	0.2358	benign	-0.18	Destabilizing	0.927	D	0.377	neutral	None	None	None	None	I
Q/C	0.6771	likely_pathogenic	0.6834	pathogenic	0.146	Stabilizing	0.999	D	0.435	neutral	None	None	None	None	I
Q/D	0.3554	ambiguous	0.3591	ambiguous	0.114	Stabilizing	0.969	D	0.328	neutral	None	None	None	None	I
Q/E	0.0977	likely_benign	0.0962	benign	0.106	Stabilizing	0.826	D	0.371	neutral	N	0.490922133	None	None	I
Q/F	0.6921	likely_pathogenic	0.7072	pathogenic	-0.29	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	I
Q/G	0.3767	ambiguous	0.3849	ambiguous	-0.396	Destabilizing	0.969	D	0.393	neutral	None	None	None	None	I
Q/H	0.1976	likely_benign	0.197	benign	-0.258	Destabilizing	0.015	N	0.131	neutral	N	0.449654301	None	None	I
Q/I	0.3416	ambiguous	0.3622	ambiguous	0.305	Stabilizing	0.997	D	0.413	neutral	None	None	None	None	I
Q/K	0.1265	likely_benign	0.1214	benign	0.056	Stabilizing	0.826	D	0.376	neutral	N	0.488631189	None	None	I
Q/L	0.1695	likely_benign	0.1814	benign	0.305	Stabilizing	0.959	D	0.371	neutral	N	0.508393173	None	None	I
Q/M	0.317	likely_benign	0.3461	ambiguous	0.454	Stabilizing	0.997	D	0.353	neutral	None	None	None	None	I
Q/N	0.2523	likely_benign	0.2637	benign	-0.32	Destabilizing	0.939	D	0.322	neutral	None	None	None	None	I
Q/P	0.3742	ambiguous	0.3916	ambiguous	0.173	Stabilizing	0.996	D	0.381	neutral	N	0.489708936	None	None	I
Q/R	0.1416	likely_benign	0.1333	benign	0.176	Stabilizing	0.92	D	0.355	neutral	N	0.44495777	None	None	I
Q/S	0.2371	likely_benign	0.2457	benign	-0.319	Destabilizing	0.969	D	0.324	neutral	None	None	None	None	I
Q/T	0.1829	likely_benign	0.1929	benign	-0.162	Destabilizing	0.969	D	0.39	neutral	None	None	None	None	I
Q/V	0.2056	likely_benign	0.2287	benign	0.173	Stabilizing	0.99	D	0.371	neutral	None	None	None	None	I
Q/W	0.6317	likely_pathogenic	0.6369	pathogenic	-0.267	Destabilizing	0.999	D	0.431	neutral	None	None	None	None	I
Q/Y	0.477	ambiguous	0.4854	ambiguous	-0.011	Destabilizing	0.939	D	0.375	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.