TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6831	20716;20717;20718	chr2:178725831;178725830;178725829	chr2:179590558;179590557;179590556
N2AB	6514	19765;19766;19767	chr2:178725831;178725830;178725829	chr2:179590558;179590557;179590556
N2A	5587	16984;16985;16986	chr2:178725831;178725830;178725829	chr2:179590558;179590557;179590556
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-52
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.1043
• Predicted PPI site: N

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/C	None	None	1.0	D	0.877	0.902	0.932833265402	gnomAD-4.0.0	1.59302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86139E-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
Y/A	0.9978	likely_pathogenic	0.9973	pathogenic	-2.493	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/C	0.9835	likely_pathogenic	0.9752	pathogenic	-1.745	Destabilizing	1.0	D	0.877	deleterious	D	0.691084021	None	None	N
Y/D	0.9986	likely_pathogenic	0.9988	pathogenic	-3.272	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.691084021	None	None	N
Y/E	0.9993	likely_pathogenic	0.9992	pathogenic	-3.025	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/F	0.2965	likely_benign	0.2423	benign	-0.923	Destabilizing	1.0	D	0.673	neutral	D	0.646701289	None	None	N
Y/G	0.9953	likely_pathogenic	0.9945	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/H	0.9909	likely_pathogenic	0.9895	pathogenic	-2.23	Highly Destabilizing	1.0	D	0.787	deleterious	D	0.690882217	None	None	N
Y/I	0.903	likely_pathogenic	0.856	pathogenic	-0.987	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9991	pathogenic	-2.096	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/L	0.894	likely_pathogenic	0.8662	pathogenic	-0.987	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
Y/M	0.9757	likely_pathogenic	0.9657	pathogenic	-1.026	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/N	0.9887	likely_pathogenic	0.9876	pathogenic	-3.056	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.691084021	None	None	N
Y/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.506	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
Y/Q	0.9993	likely_pathogenic	0.9992	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/R	0.998	likely_pathogenic	0.9978	pathogenic	-2.324	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
Y/S	0.9956	likely_pathogenic	0.9952	pathogenic	-3.33	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.691084021	None	None	N
Y/T	0.9973	likely_pathogenic	0.9962	pathogenic	-2.935	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/V	0.9197	likely_pathogenic	0.8807	pathogenic	-1.506	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.9136	likely_pathogenic	0.9017	pathogenic	-0.287	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N

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.