TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22036	66331;66332;66333	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
N2AB	20395	61408;61409;61410	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
N2A	19468	58627;58628;58629	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
N2B	12971	39136;39137;39138	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
Novex-1	13096	39511;39512;39513	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
Novex-2	13163	39712;39713;39714	chr2:178582350;178582349;178582348	chr2:179447077;179447076;179447075
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-47
• Domain position: 81
• Structural Position: 114
• Q(SASA): 0.688
• 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
Y/H	None	None	0.994	N	0.613	0.355	0.292423486923	gnomAD-4.0.0	6.86201E-07	None	None	None	None	I	None	3.00409E-05	0	None	0	0	None	0	0	0	0	0
Y/N	rs758640229	-0.024	0.994	N	0.677	0.431	0.457741393631	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
Y/N	rs758640229	-0.024	0.994	N	0.677	0.431	0.457741393631	gnomAD-4.0.0	6.86201E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01421E-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
Y/A	0.9572	likely_pathogenic	0.9498	pathogenic	-0.563	Destabilizing	0.916	D	0.639	neutral	None	None	None	None	I
Y/C	0.6804	likely_pathogenic	0.6802	pathogenic	0.118	Stabilizing	0.999	D	0.697	prob.neutral	N	0.51268898	None	None	I
Y/D	0.9432	likely_pathogenic	0.9467	pathogenic	0.981	Stabilizing	0.994	D	0.677	prob.neutral	N	0.512929211	None	None	I
Y/E	0.9841	likely_pathogenic	0.9835	pathogenic	0.957	Stabilizing	0.996	D	0.666	neutral	None	None	None	None	I
Y/F	0.1266	likely_benign	0.1226	benign	-0.294	Destabilizing	0.892	D	0.565	neutral	N	0.481539354	None	None	I
Y/G	0.9673	likely_pathogenic	0.9604	pathogenic	-0.739	Destabilizing	0.987	D	0.667	neutral	None	None	None	None	I
Y/H	0.7073	likely_pathogenic	0.6676	pathogenic	0.284	Stabilizing	0.994	D	0.613	neutral	N	0.468606853	None	None	I
Y/I	0.8049	likely_pathogenic	0.8105	pathogenic	-0.133	Destabilizing	0.073	N	0.475	neutral	None	None	None	None	I
Y/K	0.9878	likely_pathogenic	0.984	pathogenic	0.285	Stabilizing	0.987	D	0.668	neutral	None	None	None	None	I
Y/L	0.8582	likely_pathogenic	0.8542	pathogenic	-0.133	Destabilizing	0.437	N	0.602	neutral	None	None	None	None	I
Y/M	0.8752	likely_pathogenic	0.8838	pathogenic	-0.029	Destabilizing	0.993	D	0.622	neutral	None	None	None	None	I
Y/N	0.7789	likely_pathogenic	0.769	pathogenic	0.099	Stabilizing	0.994	D	0.677	prob.neutral	N	0.467592895	None	None	I
Y/P	0.9956	likely_pathogenic	0.9963	pathogenic	-0.256	Destabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	I
Y/Q	0.9721	likely_pathogenic	0.9673	pathogenic	0.142	Stabilizing	0.996	D	0.639	neutral	None	None	None	None	I
Y/R	0.9696	likely_pathogenic	0.958	pathogenic	0.522	Stabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	I
Y/S	0.9119	likely_pathogenic	0.9051	pathogenic	-0.338	Destabilizing	0.983	D	0.651	neutral	N	0.496834093	None	None	I
Y/T	0.962	likely_pathogenic	0.9582	pathogenic	-0.269	Destabilizing	0.975	D	0.639	neutral	None	None	None	None	I
Y/V	0.7938	likely_pathogenic	0.8014	pathogenic	-0.256	Destabilizing	0.653	D	0.597	neutral	None	None	None	None	I
Y/W	0.638	likely_pathogenic	0.6143	pathogenic	-0.442	Destabilizing	0.999	D	0.603	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.