TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8390	25393;25394;25395	chr2:178717706;178717705;178717704	chr2:179582433;179582432;179582431
N2AB	8073	24442;24443;24444	chr2:178717706;178717705;178717704	chr2:179582433;179582432;179582431
N2A	7146	21661;21662;21663	chr2:178717706;178717705;178717704	chr2:179582433;179582432;179582431
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-69
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6474
• 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	0.871	N	0.403	0.224	0.28798054836	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
Q/L	None	None	0.164	N	0.35	0.237	0.421550847248	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.195	likely_benign	0.2164	benign	-0.198	Destabilizing	0.222	N	0.24	neutral	None	None	None	None	I
Q/C	0.6546	likely_pathogenic	0.6839	pathogenic	0.158	Stabilizing	0.987	D	0.387	neutral	None	None	None	None	I
Q/D	0.2344	likely_benign	0.2702	benign	0.133	Stabilizing	0.164	N	0.254	neutral	None	None	None	None	I
Q/E	0.0646	likely_benign	0.0668	benign	0.11	Stabilizing	None	N	0.089	neutral	N	0.415904299	None	None	I
Q/F	0.5553	ambiguous	0.6011	pathogenic	-0.413	Destabilizing	0.926	D	0.406	neutral	None	None	None	None	I
Q/G	0.2884	likely_benign	0.3295	benign	-0.384	Destabilizing	0.567	D	0.316	neutral	None	None	None	None	I
Q/H	0.1481	likely_benign	0.1605	benign	-0.284	Destabilizing	0.871	D	0.403	neutral	N	0.517975448	None	None	I
Q/I	0.2816	likely_benign	0.2999	benign	0.202	Stabilizing	0.387	N	0.453	neutral	None	None	None	None	I
Q/K	0.0894	likely_benign	0.0926	benign	0.125	Stabilizing	0.164	N	0.281	neutral	N	0.47791555	None	None	I
Q/L	0.1101	likely_benign	0.1195	benign	0.202	Stabilizing	0.164	N	0.35	neutral	N	0.512145554	None	None	I
Q/M	0.3259	likely_benign	0.342	ambiguous	0.409	Stabilizing	0.9	D	0.409	neutral	None	None	None	None	I
Q/N	0.2218	likely_benign	0.2423	benign	-0.223	Destabilizing	0.013	N	0.138	neutral	None	None	None	None	I
Q/P	0.3757	ambiguous	0.4646	ambiguous	0.097	Stabilizing	0.593	D	0.489	neutral	N	0.496621469	None	None	I
Q/R	0.1014	likely_benign	0.1077	benign	0.241	Stabilizing	0.384	N	0.295	neutral	N	0.500677767	None	None	I
Q/S	0.212	likely_benign	0.2339	benign	-0.226	Destabilizing	0.049	N	0.114	neutral	None	None	None	None	I
Q/T	0.1553	likely_benign	0.1682	benign	-0.089	Destabilizing	0.025	N	0.355	neutral	None	None	None	None	I
Q/V	0.1868	likely_benign	0.1973	benign	0.097	Stabilizing	0.005	N	0.251	neutral	None	None	None	None	I
Q/W	0.4427	ambiguous	0.4965	ambiguous	-0.394	Destabilizing	0.997	D	0.412	neutral	None	None	None	None	I
Q/Y	0.3651	ambiguous	0.4022	ambiguous	-0.128	Destabilizing	0.975	D	0.473	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.