TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30457	91594;91595;91596	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
N2AB	28816	86671;86672;86673	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
N2A	27889	83890;83891;83892	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
N2B	21392	64399;64400;64401	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
Novex-1	21517	64774;64775;64776	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
Novex-2	21584	64975;64976;64977	chr2:178551162;178551161;178551160	chr2:179415889;179415888;179415887
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: Fn3-110
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.134
• 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/H	None	None	1.0	D	0.83	0.889	0.755256462696	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	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	0.9972	likely_pathogenic	0.998	pathogenic	-3.128	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
Y/C	0.9384	likely_pathogenic	0.9574	pathogenic	-1.996	Destabilizing	1.0	D	0.861	deleterious	D	0.642833108	None	None	N
Y/D	0.9971	likely_pathogenic	0.9981	pathogenic	-3.517	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.659054273	None	None	N
Y/E	0.9992	likely_pathogenic	0.9994	pathogenic	-3.285	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
Y/F	0.2702	likely_benign	0.2749	benign	-1.09	Destabilizing	0.999	D	0.652	neutral	D	0.568592217	None	None	N
Y/G	0.9923	likely_pathogenic	0.9941	pathogenic	-3.574	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
Y/H	0.985	likely_pathogenic	0.9884	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.83	deleterious	D	0.658448861	None	None	N
Y/I	0.9796	likely_pathogenic	0.9844	pathogenic	-1.635	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/K	0.9988	likely_pathogenic	0.9991	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.954	likely_pathogenic	0.9632	pathogenic	-1.635	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
Y/M	0.9862	likely_pathogenic	0.9896	pathogenic	-1.539	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/N	0.9808	likely_pathogenic	0.9861	pathogenic	-3.083	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.658852469	None	None	N
Y/P	0.9991	likely_pathogenic	0.9993	pathogenic	-2.151	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
Y/Q	0.9986	likely_pathogenic	0.999	pathogenic	-2.775	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Y/R	0.9958	likely_pathogenic	0.9967	pathogenic	-2.124	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9901	likely_pathogenic	0.9927	pathogenic	-3.457	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.658852469	None	None	N
Y/T	0.9965	likely_pathogenic	0.9975	pathogenic	-3.091	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/V	0.9673	likely_pathogenic	0.9744	pathogenic	-2.151	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
Y/W	0.8534	likely_pathogenic	0.8716	pathogenic	-0.311	Destabilizing	1.0	D	0.804	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.