TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8429	25510;25511;25512	chr2:178717589;178717588;178717587	chr2:179582316;179582315;179582314
N2AB	8112	24559;24560;24561	chr2:178717589;178717588;178717587	chr2:179582316;179582315;179582314
N2A	7185	21778;21779;21780	chr2:178717589;178717588;178717587	chr2:179582316;179582315;179582314
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-69
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4288
• 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/R	rs757938943	0.102	0.112	N	0.32	0.182	0.163833314356	gnomAD-2.1.1	8.08E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	8.93E-06	0
Q/R	rs757938943	0.102	0.112	N	0.32	0.182	0.163833314356	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
Q/R	rs757938943	0.102	0.112	N	0.32	0.182	0.163833314356	gnomAD-4.0.0	9.91837E-06	None	None	None	None	N	None	0	1.66806E-05	None	0	0	None	0	0	1.27167E-05	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	0.2869	likely_benign	0.2881	benign	-0.471	Destabilizing	0.017	N	0.209	neutral	None	None	None	None	N
Q/C	0.7838	likely_pathogenic	0.748	pathogenic	0.063	Stabilizing	0.987	D	0.509	neutral	None	None	None	None	N
Q/D	0.4445	ambiguous	0.4507	ambiguous	-0.924	Destabilizing	0.162	N	0.319	neutral	None	None	None	None	N
Q/E	0.0966	likely_benign	0.0995	benign	-0.866	Destabilizing	0.002	N	0.133	neutral	N	0.435818212	None	None	N
Q/F	0.655	likely_pathogenic	0.6263	pathogenic	-0.468	Destabilizing	0.859	D	0.563	neutral	None	None	None	None	N
Q/G	0.4318	ambiguous	0.4234	ambiguous	-0.779	Destabilizing	0.563	D	0.398	neutral	None	None	None	None	N
Q/H	0.2396	likely_benign	0.2223	benign	-0.86	Destabilizing	0.003	N	0.241	neutral	N	0.489346052	None	None	N
Q/I	0.3021	likely_benign	0.289	benign	0.291	Stabilizing	0.383	N	0.503	neutral	None	None	None	None	N
Q/K	0.1238	likely_benign	0.1201	benign	-0.184	Destabilizing	0.005	N	0.153	neutral	N	0.466197047	None	None	N
Q/L	0.1344	likely_benign	0.1318	benign	0.291	Stabilizing	0.162	N	0.384	neutral	N	0.474453958	None	None	N
Q/M	0.3601	ambiguous	0.3489	ambiguous	0.894	Stabilizing	0.898	D	0.459	neutral	None	None	None	None	N
Q/N	0.3086	likely_benign	0.307	benign	-0.728	Destabilizing	0.319	N	0.312	neutral	None	None	None	None	N
Q/P	0.2455	likely_benign	0.241	benign	0.068	Stabilizing	0.589	D	0.455	neutral	N	0.487921282	None	None	N
Q/R	0.1328	likely_benign	0.129	benign	-0.076	Destabilizing	0.112	N	0.32	neutral	N	0.483188084	None	None	N
Q/S	0.3254	likely_benign	0.3226	benign	-0.759	Destabilizing	0.392	N	0.293	neutral	None	None	None	None	N
Q/T	0.2261	likely_benign	0.2198	benign	-0.52	Destabilizing	0.048	N	0.387	neutral	None	None	None	None	N
Q/V	0.2252	likely_benign	0.2204	benign	0.068	Stabilizing	0.005	N	0.314	neutral	None	None	None	None	N
Q/W	0.5473	ambiguous	0.5053	ambiguous	-0.397	Destabilizing	0.997	D	0.519	neutral	None	None	None	None	N
Q/Y	0.4819	ambiguous	0.4493	ambiguous	-0.106	Destabilizing	0.753	D	0.551	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.