TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6350	19273;19274;19275	chr2:178728990;178728989;178728988	chr2:179593717;179593716;179593715
N2AB	6033	18322;18323;18324	chr2:178728990;178728989;178728988	chr2:179593717;179593716;179593715
N2A	5106	15541;15542;15543	chr2:178728990;178728989;178728988	chr2:179593717;179593716;179593715
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-47
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.2846
• 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/H	rs113892821	-1.139	0.786	N	0.448	0.173	0.176091768786	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
Q/H	rs113892821	-1.139	0.786	N	0.448	0.173	0.176091768786	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Q/H	rs113892821	-1.139	0.786	N	0.448	0.173	0.176091768786	gnomAD-4.0.0	1.23992E-06	None	None	None	None	N	None	0	1.66939E-05	None	0	0	None	0	0	0	1.09859E-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
Q/A	0.2766	likely_benign	0.2842	benign	-0.92	Destabilizing	0.2	N	0.353	neutral	None	None	None	None	N
Q/C	0.5566	ambiguous	0.5609	ambiguous	-0.315	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	N
Q/D	0.3974	ambiguous	0.418	ambiguous	-0.681	Destabilizing	0.223	N	0.409	neutral	None	None	None	None	N
Q/E	0.09	likely_benign	0.0899	benign	-0.525	Destabilizing	0.006	N	0.244	neutral	N	0.506582232	None	None	N
Q/F	0.5601	ambiguous	0.5779	pathogenic	-0.543	Destabilizing	0.41	N	0.554	neutral	None	None	None	None	N
Q/G	0.3459	ambiguous	0.3585	ambiguous	-1.304	Destabilizing	0.365	N	0.433	neutral	None	None	None	None	N
Q/H	0.1506	likely_benign	0.1546	benign	-1.023	Destabilizing	0.786	D	0.448	neutral	N	0.472683089	None	None	N
Q/I	0.3338	likely_benign	0.3408	ambiguous	0.086	Stabilizing	0.582	D	0.548	neutral	None	None	None	None	N
Q/K	0.0928	likely_benign	0.0919	benign	-0.229	Destabilizing	None	N	0.271	neutral	N	0.481513216	None	None	N
Q/L	0.1487	likely_benign	0.1526	benign	0.086	Stabilizing	0.178	N	0.406	neutral	N	0.515548432	None	None	N
Q/M	0.3511	ambiguous	0.3614	ambiguous	0.469	Stabilizing	0.968	D	0.414	neutral	None	None	None	None	N
Q/N	0.281	likely_benign	0.2932	benign	-0.864	Destabilizing	0.365	N	0.444	neutral	None	None	None	None	N
Q/P	0.7706	likely_pathogenic	0.7977	pathogenic	-0.22	Destabilizing	0.68	D	0.525	neutral	D	0.52948539	None	None	N
Q/R	0.0938	likely_benign	0.0951	benign	-0.25	Destabilizing	0.001	N	0.281	neutral	N	0.495671805	None	None	N
Q/S	0.2748	likely_benign	0.2788	benign	-1.111	Destabilizing	0.111	N	0.374	neutral	None	None	None	None	N
Q/T	0.1889	likely_benign	0.191	benign	-0.746	Destabilizing	0.008	N	0.27	neutral	None	None	None	None	N
Q/V	0.2468	likely_benign	0.248	benign	-0.22	Destabilizing	0.365	N	0.452	neutral	None	None	None	None	N
Q/W	0.4092	ambiguous	0.4206	ambiguous	-0.351	Destabilizing	0.908	D	0.54	neutral	None	None	None	None	N
Q/Y	0.3483	ambiguous	0.3618	ambiguous	-0.102	Destabilizing	0.002	N	0.27	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.