TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32644	98155;98156;98157	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
N2AB	31003	93232;93233;93234	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
N2A	30076	90451;90452;90453	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
N2B	23579	70960;70961;70962	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
Novex-1	23704	71335;71336;71337	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
Novex-2	23771	71536;71537;71538	chr2:178540236;178540235;178540234	chr2:179404963;179404962;179404961
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: Fn3-126
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.4127
• 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	rs773841779	-0.789	0.999	N	0.434	0.239	0.184867976434	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.22544E-04	None	0	None	0	0	0
Q/H	rs773841779	-0.789	0.999	N	0.434	0.239	0.184867976434	gnomAD-4.0.0	3.42098E-06	None	None	None	None	N	None	0	0	None	0	1.25945E-04	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	0.2337	likely_benign	0.2404	benign	-0.414	Destabilizing	0.997	D	0.329	neutral	None	None	None	None	N
Q/C	0.5941	likely_pathogenic	0.65	pathogenic	0.3	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
Q/D	0.364	ambiguous	0.4208	ambiguous	-0.494	Destabilizing	0.997	D	0.321	neutral	None	None	None	None	N
Q/E	0.1	likely_benign	0.1082	benign	-0.473	Destabilizing	0.992	D	0.296	neutral	N	0.365786831	None	None	N
Q/F	0.7628	likely_pathogenic	0.7947	pathogenic	-0.319	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
Q/G	0.2646	likely_benign	0.3038	benign	-0.701	Destabilizing	0.997	D	0.381	neutral	None	None	None	None	N
Q/H	0.2715	likely_benign	0.3167	benign	-0.729	Destabilizing	0.999	D	0.434	neutral	N	0.442575534	None	None	N
Q/I	0.4978	ambiguous	0.5197	ambiguous	0.285	Stabilizing	0.999	D	0.593	neutral	None	None	None	None	N
Q/K	0.135	likely_benign	0.159	benign	-0.338	Destabilizing	0.997	D	0.297	neutral	N	0.449424148	None	None	N
Q/L	0.1941	likely_benign	0.2124	benign	0.285	Stabilizing	0.997	D	0.381	neutral	N	0.488078537	None	None	N
Q/M	0.3848	ambiguous	0.3886	ambiguous	0.769	Stabilizing	0.999	D	0.437	neutral	None	None	None	None	N
Q/N	0.2906	likely_benign	0.3047	benign	-0.574	Destabilizing	0.999	D	0.387	neutral	None	None	None	None	N
Q/P	0.6887	likely_pathogenic	0.7719	pathogenic	0.082	Stabilizing	0.999	D	0.469	neutral	N	0.447962711	None	None	N
Q/R	0.1383	likely_benign	0.1789	benign	-0.208	Destabilizing	0.997	D	0.326	neutral	N	0.40640409	None	None	N
Q/S	0.2304	likely_benign	0.2286	benign	-0.589	Destabilizing	0.997	D	0.273	neutral	None	None	None	None	N
Q/T	0.184	likely_benign	0.1908	benign	-0.408	Destabilizing	0.999	D	0.416	neutral	None	None	None	None	N
Q/V	0.3047	likely_benign	0.3339	benign	0.082	Stabilizing	0.999	D	0.444	neutral	None	None	None	None	N
Q/W	0.6809	likely_pathogenic	0.7901	pathogenic	-0.276	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
Q/Y	0.5513	ambiguous	0.6375	pathogenic	-0.071	Destabilizing	0.999	D	0.444	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.