TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27005	81238;81239;81240	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
N2AB	25364	76315;76316;76317	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
N2A	24437	73534;73535;73536	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
N2B	17940	54043;54044;54045	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
Novex-1	18065	54418;54419;54420	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
Novex-2	18132	54619;54620;54621	chr2:178565119;178565118;178565117	chr2:179429846;179429845;179429844
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-84
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.2038
• 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
I/K	rs1430969967	-1.744	0.983	D	0.842	0.666	0.87933222287	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
I/T	rs1430969967	-2.12	0.892	D	0.794	0.61	0.749266289315	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/T	rs1430969967	-2.12	0.892	D	0.794	0.61	0.749266289315	gnomAD-4.0.0	2.05299E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69879E-06	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
I/A	0.9729	likely_pathogenic	0.9758	pathogenic	-2.364	Highly Destabilizing	0.845	D	0.665	neutral	None	None	None	None	I
I/C	0.9835	likely_pathogenic	0.9841	pathogenic	-1.386	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	I
I/D	0.9985	likely_pathogenic	0.9988	pathogenic	-2.38	Highly Destabilizing	0.996	D	0.85	deleterious	None	None	None	None	I
I/E	0.9951	likely_pathogenic	0.996	pathogenic	-2.327	Highly Destabilizing	0.987	D	0.844	deleterious	None	None	None	None	I
I/F	0.9099	likely_pathogenic	0.9218	pathogenic	-1.744	Destabilizing	0.975	D	0.755	deleterious	None	None	None	None	I
I/G	0.9955	likely_pathogenic	0.9962	pathogenic	-2.76	Highly Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	I
I/H	0.9964	likely_pathogenic	0.9969	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
I/K	0.9902	likely_pathogenic	0.9924	pathogenic	-1.719	Destabilizing	0.983	D	0.842	deleterious	D	0.540923239	None	None	I
I/L	0.4482	ambiguous	0.4757	ambiguous	-1.291	Destabilizing	0.426	N	0.443	neutral	N	0.474983771	None	None	I
I/M	0.6051	likely_pathogenic	0.5769	pathogenic	-0.855	Destabilizing	0.983	D	0.72	prob.delet.	D	0.52476754	None	None	I
I/N	0.9659	likely_pathogenic	0.97	pathogenic	-1.61	Destabilizing	0.996	D	0.846	deleterious	None	None	None	None	I
I/P	0.9516	likely_pathogenic	0.9631	pathogenic	-1.623	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	I
I/Q	0.993	likely_pathogenic	0.9939	pathogenic	-1.764	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	I
I/R	0.9886	likely_pathogenic	0.9911	pathogenic	-1.083	Destabilizing	0.983	D	0.847	deleterious	D	0.525781498	None	None	I
I/S	0.9793	likely_pathogenic	0.9828	pathogenic	-2.205	Highly Destabilizing	0.987	D	0.818	deleterious	None	None	None	None	I
I/T	0.9397	likely_pathogenic	0.9551	pathogenic	-2.035	Highly Destabilizing	0.892	D	0.794	deleterious	D	0.54016277	None	None	I
I/V	0.1325	likely_benign	0.1424	benign	-1.623	Destabilizing	0.011	N	0.266	neutral	N	0.491817849	None	None	I
I/W	0.9984	likely_pathogenic	0.9984	pathogenic	-1.944	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
I/Y	0.9873	likely_pathogenic	0.9889	pathogenic	-1.743	Destabilizing	0.987	D	0.8	deleterious	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.