TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22282	67069;67070;67071	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
N2AB	20641	62146;62147;62148	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
N2A	19714	59365;59366;59367	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
N2B	13217	39874;39875;39876	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
Novex-1	13342	40249;40250;40251	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
Novex-2	13409	40450;40451;40452	chr2:178580535;178580534;178580533	chr2:179445262;179445261;179445260
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: Ig-126
• Domain position: 18
• Structural Position: 31
• Q(SASA): 0.3247
• 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	rs745992545	-0.151	0.998	N	0.663	0.299	None	gnomAD-2.1.1	2.87E-05	None	None	None	None	I	None	3.31181E-04	0	None	0	0	None	0	None	0	0	0
Y/H	rs745992545	-0.151	0.998	N	0.663	0.299	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	I	None	3.61829E-04	0	0	0	0	None	0	0	0	0	0
Y/H	rs745992545	-0.151	0.998	N	0.663	0.299	None	gnomAD-4.0.0	1.67421E-05	None	None	None	None	I	None	3.60567E-04	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
Y/A	0.7923	likely_pathogenic	0.7661	pathogenic	-1.626	Destabilizing	0.968	D	0.607	neutral	None	None	None	None	I
Y/C	0.3487	ambiguous	0.3144	benign	-0.587	Destabilizing	0.999	D	0.719	prob.delet.	N	0.500427051	None	None	I
Y/D	0.8446	likely_pathogenic	0.8067	pathogenic	0.005	Stabilizing	0.998	D	0.753	deleterious	N	0.453883898	None	None	I
Y/E	0.9468	likely_pathogenic	0.9329	pathogenic	0.068	Stabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	I
Y/F	0.144	likely_benign	0.1465	benign	-0.619	Destabilizing	0.067	N	0.397	neutral	N	0.438031798	None	None	I
Y/G	0.8034	likely_pathogenic	0.76	pathogenic	-1.907	Destabilizing	0.995	D	0.728	prob.delet.	None	None	None	None	I
Y/H	0.4189	ambiguous	0.3906	ambiguous	-0.389	Destabilizing	0.998	D	0.663	neutral	N	0.434626133	None	None	I
Y/I	0.7669	likely_pathogenic	0.7247	pathogenic	-0.811	Destabilizing	0.982	D	0.677	prob.neutral	None	None	None	None	I
Y/K	0.9221	likely_pathogenic	0.8916	pathogenic	-0.705	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	I
Y/L	0.6607	likely_pathogenic	0.6284	pathogenic	-0.811	Destabilizing	0.938	D	0.534	neutral	None	None	None	None	I
Y/M	0.8002	likely_pathogenic	0.769	pathogenic	-0.624	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
Y/N	0.5614	ambiguous	0.4924	ambiguous	-1.073	Destabilizing	0.998	D	0.742	deleterious	N	0.471776225	None	None	I
Y/P	0.9647	likely_pathogenic	0.9528	pathogenic	-1.072	Destabilizing	0.998	D	0.744	deleterious	None	None	None	None	I
Y/Q	0.8659	likely_pathogenic	0.8363	pathogenic	-0.95	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	I
Y/R	0.7948	likely_pathogenic	0.7464	pathogenic	-0.366	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
Y/S	0.548	ambiguous	0.4933	ambiguous	-1.576	Destabilizing	0.994	D	0.725	prob.delet.	N	0.423291632	None	None	I
Y/T	0.7813	likely_pathogenic	0.7342	pathogenic	-1.416	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	I
Y/V	0.6563	likely_pathogenic	0.6191	pathogenic	-1.072	Destabilizing	0.968	D	0.642	neutral	None	None	None	None	I
Y/W	0.5909	likely_pathogenic	0.5478	ambiguous	-0.388	Destabilizing	1.0	D	0.638	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.