TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10057	30394;30395;30396	chr2:178704201;178704200;178704199	chr2:179568928;179568927;179568926
N2AB	9740	29443;29444;29445	chr2:178704201;178704200;178704199	chr2:179568928;179568927;179568926
N2A	8813	26662;26663;26664	chr2:178704201;178704200;178704199	chr2:179568928;179568927;179568926
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: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-85
• Domain position: 69
• Structural Position: 153
• Q(SASA): 0.5409
• 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/P	None	None	0.106	None	0.523	0.23	0.202086224978	gnomAD-4.0.0	4.10489E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.3964E-06	0	0
Q/R	rs2075483683	None	None	None	0.16	0.102	0.0611884634855	gnomAD-4.0.0	6.84148E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.994E-07	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	0.2092	likely_benign	0.2659	benign	-0.63	Destabilizing	0.016	N	0.388	neutral	None	None	None	None	N
Q/C	0.5838	likely_pathogenic	0.5972	pathogenic	-0.03	Destabilizing	0.864	D	0.477	neutral	None	None	None	None	N
Q/D	0.4374	ambiguous	0.5601	ambiguous	-0.805	Destabilizing	0.016	N	0.439	neutral	None	None	None	None	N
Q/E	0.0976	likely_benign	0.125	benign	-0.74	Destabilizing	None	N	0.179	neutral	None	None	None	None	N
Q/F	0.5475	ambiguous	0.6119	pathogenic	-0.573	Destabilizing	0.356	N	0.499	neutral	None	None	None	None	N
Q/G	0.311	likely_benign	0.4194	ambiguous	-0.945	Destabilizing	0.031	N	0.476	neutral	None	None	None	None	N
Q/H	0.1828	likely_benign	0.2168	benign	-0.964	Destabilizing	None	N	0.229	neutral	None	None	None	None	N
Q/I	0.249	likely_benign	0.2971	benign	0.156	Stabilizing	0.356	N	0.54	neutral	None	None	None	None	N
Q/K	0.0697	likely_benign	0.0809	benign	-0.235	Destabilizing	None	N	0.177	neutral	None	None	None	None	N
Q/L	0.1104	likely_benign	0.1368	benign	0.156	Stabilizing	0.055	N	0.509	neutral	None	None	None	None	N
Q/M	0.281	likely_benign	0.3441	ambiguous	0.723	Stabilizing	0.628	D	0.493	neutral	None	None	None	None	N
Q/N	0.2712	likely_benign	0.3302	benign	-0.784	Destabilizing	0.038	N	0.434	neutral	None	None	None	None	N
Q/P	0.2236	likely_benign	0.3115	benign	-0.076	Destabilizing	0.106	N	0.523	neutral	None	None	None	None	N
Q/R	0.0771	likely_benign	0.076	benign	-0.138	Destabilizing	None	N	0.16	neutral	None	None	None	None	N
Q/S	0.2505	likely_benign	0.3147	benign	-0.839	Destabilizing	0.016	N	0.441	neutral	None	None	None	None	N
Q/T	0.1615	likely_benign	0.1928	benign	-0.586	Destabilizing	0.072	N	0.505	neutral	None	None	None	None	N
Q/V	0.1977	likely_benign	0.2216	benign	-0.076	Destabilizing	0.072	N	0.508	neutral	None	None	None	None	N
Q/W	0.3653	ambiguous	0.413	ambiguous	-0.459	Destabilizing	0.864	D	0.492	neutral	None	None	None	None	N
Q/Y	0.3764	ambiguous	0.4399	ambiguous	-0.198	Destabilizing	0.12	N	0.565	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.