TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3292	10099;10100;10101	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
N2AB	3292	10099;10100;10101	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
N2A	3292	10099;10100;10101	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
N2B	3246	9961;9962;9963	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
Novex-1	3246	9961;9962;9963	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
Novex-2	3246	9961;9962;9963	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366
Novex-3	3292	10099;10100;10101	chr2:178764641;178764640;178764639	chr2:179629368;179629367;179629366

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-23
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.4079
• 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
Q/K	None	None	0.826	N	0.314	0.307	0.281780670237	gnomAD-4.0.0	1.59053E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
Q/R	rs794729586	0.042	0.92	N	0.258	0.335	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.82E-06	0
Q/R	rs794729586	0.042	0.92	N	0.258	0.335	None	gnomAD-4.0.0	4.77161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.56952E-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	0.3317	likely_benign	0.3534	ambiguous	-0.423	Destabilizing	0.863	D	0.371	neutral	None	None	None	None	N
Q/C	0.8353	likely_pathogenic	0.871	pathogenic	0.01	Stabilizing	0.999	D	0.526	neutral	None	None	None	None	N
Q/D	0.3347	likely_benign	0.3823	ambiguous	0.25	Stabilizing	0.759	D	0.285	neutral	None	None	None	None	N
Q/E	0.0811	likely_benign	0.0925	benign	0.335	Stabilizing	0.021	N	0.119	neutral	N	0.465043481	None	None	N
Q/F	0.8378	likely_pathogenic	0.8605	pathogenic	-0.26	Destabilizing	0.997	D	0.524	neutral	None	None	None	None	N
Q/G	0.3475	ambiguous	0.3924	ambiguous	-0.731	Destabilizing	0.863	D	0.445	neutral	None	None	None	None	N
Q/H	0.3254	likely_benign	0.346	ambiguous	-0.343	Destabilizing	0.988	D	0.434	neutral	N	0.514335296	None	None	N
Q/I	0.6205	likely_pathogenic	0.6721	pathogenic	0.337	Stabilizing	0.997	D	0.533	neutral	None	None	None	None	N
Q/K	0.109	likely_benign	0.1323	benign	0.1	Stabilizing	0.826	D	0.314	neutral	N	0.503714813	None	None	N
Q/L	0.2042	likely_benign	0.2303	benign	0.337	Stabilizing	0.959	D	0.454	neutral	N	0.517785275	None	None	N
Q/M	0.4679	ambiguous	0.4874	ambiguous	0.443	Stabilizing	0.997	D	0.441	neutral	None	None	None	None	N
Q/N	0.254	likely_benign	0.268	benign	-0.542	Destabilizing	0.079	N	0.113	neutral	None	None	None	None	N
Q/P	0.2704	likely_benign	0.3173	benign	0.114	Stabilizing	0.986	D	0.437	neutral	N	0.518577433	None	None	N
Q/R	0.1314	likely_benign	0.1558	benign	0.165	Stabilizing	0.92	D	0.258	neutral	N	0.500562266	None	None	N
Q/S	0.315	likely_benign	0.3222	benign	-0.659	Destabilizing	0.863	D	0.297	neutral	None	None	None	None	N
Q/T	0.3001	likely_benign	0.3154	benign	-0.373	Destabilizing	0.939	D	0.35	neutral	None	None	None	None	N
Q/V	0.4825	ambiguous	0.5162	ambiguous	0.114	Stabilizing	0.969	D	0.488	neutral	None	None	None	None	N
Q/W	0.7137	likely_pathogenic	0.7819	pathogenic	-0.151	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
Q/Y	0.6397	likely_pathogenic	0.6896	pathogenic	0.104	Stabilizing	0.997	D	0.467	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.