TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9466	28621;28622;28623	chr2:178710701;178710700;178710699	chr2:179575428;179575427;179575426
N2AB	9149	27670;27671;27672	chr2:178710701;178710700;178710699	chr2:179575428;179575427;179575426
N2A	8222	24889;24890;24891	chr2:178710701;178710700;178710699	chr2:179575428;179575427;179575426
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-80
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3494
• 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	None	None	0.151	0.229	0.126345400529	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99442E-07	0	1.65711E-05
Q/P	rs1215467586	-0.066	0.523	None	0.505	0.359	0.375326005269	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Q/P	rs1215467586	-0.066	0.523	None	0.505	0.359	0.375326005269	gnomAD-4.0.0	1.36865E-06	None	None	None	None	N	None	5.97693E-05	0	None	0	0	None	0	0	0	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	0.1928	likely_benign	0.2342	benign	-0.531	Destabilizing	0.129	N	0.382	neutral	None	None	None	None	N
Q/C	0.5649	likely_pathogenic	0.72	pathogenic	0.09	Stabilizing	0.983	D	0.54	neutral	None	None	None	None	N
Q/D	0.3185	likely_benign	0.3939	ambiguous	-0.786	Destabilizing	0.129	N	0.369	neutral	None	None	None	None	N
Q/E	0.0927	likely_benign	0.0906	benign	-0.734	Destabilizing	0.001	N	0.127	neutral	None	None	None	None	N
Q/F	0.4742	ambiguous	0.6001	pathogenic	-0.481	Destabilizing	0.94	D	0.539	neutral	None	None	None	None	N
Q/G	0.2764	likely_benign	0.3624	ambiguous	-0.841	Destabilizing	0.228	N	0.462	neutral	None	None	None	None	N
Q/H	0.172	likely_benign	0.219	benign	-0.914	Destabilizing	0.794	D	0.475	neutral	None	None	None	None	N
Q/I	0.2145	likely_benign	0.2584	benign	0.238	Stabilizing	0.836	D	0.566	neutral	None	None	None	None	N
Q/K	0.0893	likely_benign	0.1038	benign	-0.257	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
Q/L	0.0955	likely_benign	0.1105	benign	0.238	Stabilizing	0.351	N	0.487	neutral	None	None	None	None	N
Q/M	0.2457	likely_benign	0.2889	benign	0.821	Stabilizing	0.94	D	0.482	neutral	None	None	None	None	N
Q/N	0.2065	likely_benign	0.2521	benign	-0.755	Destabilizing	0.418	N	0.354	neutral	None	None	None	None	N
Q/P	0.1692	likely_benign	0.235	benign	0.013	Stabilizing	0.523	D	0.505	neutral	None	None	None	None	N
Q/R	0.1006	likely_benign	0.1235	benign	-0.166	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	N
Q/S	0.1999	likely_benign	0.2571	benign	-0.775	Destabilizing	0.129	N	0.371	neutral	None	None	None	None	N
Q/T	0.1483	likely_benign	0.1738	benign	-0.54	Destabilizing	0.418	N	0.45	neutral	None	None	None	None	N
Q/V	0.168	likely_benign	0.2025	benign	0.013	Stabilizing	0.418	N	0.485	neutral	None	None	None	None	N
Q/W	0.3885	ambiguous	0.5366	ambiguous	-0.394	Destabilizing	0.983	D	0.55	neutral	None	None	None	None	N
Q/Y	0.3357	likely_benign	0.4541	ambiguous	-0.136	Destabilizing	0.94	D	0.532	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.