TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8256	24991;24992;24993	chr2:178718340;178718339;178718338	chr2:179583067;179583066;179583065
N2AB	7939	24040;24041;24042	chr2:178718340;178718339;178718338	chr2:179583067;179583066;179583065
N2A	7012	21259;21260;21261	chr2:178718340;178718339;178718338	chr2:179583067;179583066;179583065
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-67
• Domain position: 86
• Structural Position: 172
• Q(SASA): 0.1494
• 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
A/T	rs772515770	-1.492	0.865	N	0.577	0.425	0.476051820916	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
A/T	rs772515770	-1.492	0.865	N	0.577	0.425	0.476051820916	gnomAD-4.0.0	1.59221E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
A/V	rs879112949	None	0.928	N	0.647	0.362	None	gnomAD-4.0.0	1.59218E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86E-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
A/C	0.8018	likely_pathogenic	0.7868	pathogenic	-1.402	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	I
A/D	0.9588	likely_pathogenic	0.9479	pathogenic	-2.085	Highly Destabilizing	0.978	D	0.847	deleterious	D	0.551079727	None	None	I
A/E	0.9642	likely_pathogenic	0.9563	pathogenic	-2.025	Highly Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	I
A/F	0.9165	likely_pathogenic	0.9043	pathogenic	-1.082	Destabilizing	0.992	D	0.901	deleterious	None	None	None	None	I
A/G	0.157	likely_benign	0.1588	benign	-1.5	Destabilizing	0.865	D	0.525	neutral	N	0.490588444	None	None	I
A/H	0.9763	likely_pathogenic	0.9745	pathogenic	-1.734	Destabilizing	0.998	D	0.878	deleterious	None	None	None	None	I
A/I	0.8625	likely_pathogenic	0.8056	pathogenic	-0.294	Destabilizing	0.992	D	0.86	deleterious	None	None	None	None	I
A/K	0.9875	likely_pathogenic	0.9869	pathogenic	-1.409	Destabilizing	0.968	D	0.807	deleterious	None	None	None	None	I
A/L	0.7856	likely_pathogenic	0.745	pathogenic	-0.294	Destabilizing	0.944	D	0.739	prob.delet.	None	None	None	None	I
A/M	0.7866	likely_pathogenic	0.7372	pathogenic	-0.405	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
A/N	0.8917	likely_pathogenic	0.8847	pathogenic	-1.41	Destabilizing	0.968	D	0.87	deleterious	None	None	None	None	I
A/P	0.9918	likely_pathogenic	0.9883	pathogenic	-0.536	Destabilizing	0.989	D	0.859	deleterious	D	0.551079727	None	None	I
A/Q	0.9529	likely_pathogenic	0.9508	pathogenic	-1.465	Destabilizing	0.983	D	0.868	deleterious	None	None	None	None	I
A/R	0.9726	likely_pathogenic	0.9725	pathogenic	-1.177	Destabilizing	0.983	D	0.861	deleterious	None	None	None	None	I
A/S	0.1783	likely_benign	0.1847	benign	-1.796	Destabilizing	0.146	N	0.32	neutral	N	0.511704439	None	None	I
A/T	0.3196	likely_benign	0.2959	benign	-1.63	Destabilizing	0.865	D	0.577	neutral	N	0.505855089	None	None	I
A/V	0.5656	likely_pathogenic	0.4901	ambiguous	-0.536	Destabilizing	0.928	D	0.647	neutral	N	0.497115222	None	None	I
A/W	0.9936	likely_pathogenic	0.9923	pathogenic	-1.59	Destabilizing	0.999	D	0.893	deleterious	None	None	None	None	I
A/Y	0.9603	likely_pathogenic	0.956	pathogenic	-1.127	Destabilizing	0.997	D	0.899	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.