TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21150	63673;63674;63675	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
N2AB	19509	58750;58751;58752	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
N2A	18582	55969;55970;55971	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
N2B	12085	36478;36479;36480	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
Novex-1	12210	36853;36854;36855	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
Novex-2	12277	37054;37055;37056	chr2:178587959;178587958;178587957	chr2:179452686;179452685;179452684
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: Fn3-41
• Domain position: 87
• Structural Position: 113
• Q(SASA): 0.8518
• 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	0.999	N	0.563	0.285	0.188950314367	gnomAD-4.0.0	6.85493E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00469E-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	0.2332	likely_benign	0.2356	benign	-0.1	Destabilizing	0.997	D	0.511	neutral	None	None	None	None	I
Q/C	0.847	likely_pathogenic	0.8502	pathogenic	0.026	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	I
Q/D	0.6625	likely_pathogenic	0.6526	pathogenic	0.023	Stabilizing	0.997	D	0.538	neutral	None	None	None	None	I
Q/E	0.1279	likely_benign	0.1182	benign	-0.012	Destabilizing	0.992	D	0.391	neutral	N	0.434420197	None	None	I
Q/F	0.8638	likely_pathogenic	0.8621	pathogenic	-0.392	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	I
Q/G	0.4645	ambiguous	0.4715	ambiguous	-0.255	Destabilizing	0.997	D	0.479	neutral	None	None	None	None	I
Q/H	0.4901	ambiguous	0.492	ambiguous	-0.084	Destabilizing	0.999	D	0.563	neutral	N	0.518500231	None	None	I
Q/I	0.4417	ambiguous	0.4326	ambiguous	0.214	Stabilizing	0.999	D	0.598	neutral	None	None	None	None	I
Q/K	0.1829	likely_benign	0.1791	benign	0.079	Stabilizing	0.997	D	0.457	neutral	N	0.446271987	None	None	I
Q/L	0.2319	likely_benign	0.2304	benign	0.214	Stabilizing	0.997	D	0.479	neutral	N	0.481675427	None	None	I
Q/M	0.4023	ambiguous	0.4004	ambiguous	0.256	Stabilizing	0.999	D	0.563	neutral	None	None	None	None	I
Q/N	0.4836	ambiguous	0.4876	ambiguous	-0.301	Destabilizing	0.999	D	0.541	neutral	None	None	None	None	I
Q/P	0.3345	likely_benign	0.32	benign	0.136	Stabilizing	0.999	D	0.555	neutral	N	0.478981838	None	None	I
Q/R	0.2047	likely_benign	0.2007	benign	0.241	Stabilizing	0.997	D	0.526	neutral	N	0.461606799	None	None	I
Q/S	0.3168	likely_benign	0.3293	benign	-0.256	Destabilizing	0.997	D	0.505	neutral	None	None	None	None	I
Q/T	0.2867	likely_benign	0.2851	benign	-0.146	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	I
Q/V	0.2915	likely_benign	0.2855	benign	0.136	Stabilizing	0.999	D	0.465	neutral	None	None	None	None	I
Q/W	0.8617	likely_pathogenic	0.852	pathogenic	-0.428	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
Q/Y	0.7516	likely_pathogenic	0.7479	pathogenic	-0.143	Destabilizing	0.999	D	0.544	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.