TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28225	84898;84899;84900	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
N2AB	26584	79975;79976;79977	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
N2A	25657	77194;77195;77196	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
N2B	19160	57703;57704;57705	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
Novex-1	19285	58078;58079;58080	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
Novex-2	19352	58279;58280;58281	chr2:178561459;178561458;178561457	chr2:179426186;179426185;179426184
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: Fn3-93
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.1046
• 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	rs1703630700	None	1.0	D	0.876	0.918	0.87005058023	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1703630700	None	1.0	D	0.876	0.918	0.87005058023	gnomAD-4.0.0	6.57125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-05	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	0.9889	likely_pathogenic	0.9901	pathogenic	-3.246	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Y/C	0.904	likely_pathogenic	0.907	pathogenic	-1.97	Destabilizing	1.0	D	0.876	deleterious	D	0.675489706	None	None	N
Y/D	0.9942	likely_pathogenic	0.9934	pathogenic	-3.86	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.675489706	None	None	N
Y/E	0.9974	likely_pathogenic	0.997	pathogenic	-3.66	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/F	0.2827	likely_benign	0.2911	benign	-1.3	Destabilizing	0.999	D	0.762	deleterious	D	0.62538322	None	None	N
Y/G	0.9709	likely_pathogenic	0.9739	pathogenic	-3.646	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9511	likely_pathogenic	0.9466	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.675489706	None	None	N
Y/I	0.9652	likely_pathogenic	0.9661	pathogenic	-1.901	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/K	0.9954	likely_pathogenic	0.9948	pathogenic	-2.597	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/L	0.9068	likely_pathogenic	0.9151	pathogenic	-1.901	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
Y/M	0.9757	likely_pathogenic	0.9772	pathogenic	-1.56	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/N	0.9594	likely_pathogenic	0.9536	pathogenic	-3.44	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.675287902	None	None	N
Y/P	0.9974	likely_pathogenic	0.9977	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
Y/Q	0.995	likely_pathogenic	0.9943	pathogenic	-3.184	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/R	0.9841	likely_pathogenic	0.9822	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/S	0.9782	likely_pathogenic	0.9779	pathogenic	-3.707	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.649951594	None	None	N
Y/T	0.9916	likely_pathogenic	0.9916	pathogenic	-3.393	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/V	0.9253	likely_pathogenic	0.9269	pathogenic	-2.366	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/W	0.8181	likely_pathogenic	0.8204	pathogenic	-0.699	Destabilizing	1.0	D	0.833	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.