TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5708	17347;17348;17349	chr2:178731753;178731752;178731751	chr2:179596480;179596479;179596478
N2AB	5391	16396;16397;16398	chr2:178731753;178731752;178731751	chr2:179596480;179596479;179596478
N2A	4464	13615;13616;13617	chr2:178731753;178731752;178731751	chr2:179596480;179596479;179596478
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-40
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.2197
• 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	rs373282814	-1.067	0.998	N	0.487	0.216	0.261217442401	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	1.24018E-04	0	None	0	0	None	0	None	0	0	0
Q/H	rs373282814	-1.067	0.998	N	0.487	0.216	0.261217442401	gnomAD-3.1.2	5.91E-05	None	None	None	None	I	None	2.17171E-04	0	0	0	0	None	0	0	0	0	0
Q/H	rs373282814	-1.067	0.998	N	0.487	0.216	0.261217442401	gnomAD-4.0.0	6.84231E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15947E-05	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	0.2782	likely_benign	0.2696	benign	-1.173	Destabilizing	0.864	D	0.482	neutral	None	None	None	None	I
Q/C	0.4778	ambiguous	0.4704	ambiguous	-0.762	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
Q/D	0.4939	ambiguous	0.501	ambiguous	-1.989	Destabilizing	0.939	D	0.519	neutral	None	None	None	None	I
Q/E	0.0962	likely_benign	0.0979	benign	-1.713	Destabilizing	0.238	N	0.28	neutral	N	0.433696974	None	None	I
Q/F	0.5497	ambiguous	0.5285	ambiguous	-0.662	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
Q/G	0.3548	ambiguous	0.3428	ambiguous	-1.609	Destabilizing	0.969	D	0.529	neutral	None	None	None	None	I
Q/H	0.147	likely_benign	0.1526	benign	-1.205	Destabilizing	0.998	D	0.487	neutral	N	0.454033046	None	None	I
Q/I	0.2947	likely_benign	0.2861	benign	0.016	Stabilizing	0.995	D	0.609	neutral	None	None	None	None	I
Q/K	0.1082	likely_benign	0.1094	benign	-0.504	Destabilizing	0.828	D	0.538	neutral	N	0.474562161	None	None	I
Q/L	0.146	likely_benign	0.136	benign	0.016	Stabilizing	0.979	D	0.497	neutral	N	0.506519864	None	None	I
Q/M	0.3572	ambiguous	0.3427	ambiguous	0.208	Stabilizing	0.999	D	0.495	neutral	None	None	None	None	I
Q/N	0.297	likely_benign	0.2995	benign	-1.385	Destabilizing	0.969	D	0.463	neutral	None	None	None	None	I
Q/P	0.8637	likely_pathogenic	0.8497	pathogenic	-0.355	Destabilizing	0.994	D	0.513	neutral	N	0.486380442	None	None	I
Q/R	0.0999	likely_benign	0.0986	benign	-0.657	Destabilizing	0.068	N	0.461	neutral	N	0.472425933	None	None	I
Q/S	0.2546	likely_benign	0.2374	benign	-1.635	Destabilizing	0.546	D	0.341	neutral	None	None	None	None	I
Q/T	0.1817	likely_benign	0.1753	benign	-1.167	Destabilizing	0.939	D	0.475	neutral	None	None	None	None	I
Q/V	0.2204	likely_benign	0.2099	benign	-0.355	Destabilizing	0.984	D	0.55	neutral	None	None	None	None	I
Q/W	0.4896	ambiguous	0.475	ambiguous	-0.682	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
Q/Y	0.3414	ambiguous	0.3333	benign	-0.31	Destabilizing	0.999	D	0.522	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.