TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9971	30136;30137;30138	chr2:178704561;178704560;178704559	chr2:179569288;179569287;179569286
N2AB	9654	29185;29186;29187	chr2:178704561;178704560;178704559	chr2:179569288;179569287;179569286
N2A	8727	26404;26405;26406	chr2:178704561;178704560;178704559	chr2:179569288;179569287;179569286
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: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-84
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.1021
• 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/F	None	None	0.008	None	0.451	0.454	0.48087575253	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.4108E-04	0	0	0
Y/H	rs1471839553	-2.225	0.983	None	0.734	0.81	0.636259158049	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	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	0.9983	likely_pathogenic	0.9985	pathogenic	-2.018	Highly Destabilizing	0.633	D	0.823	deleterious	None	None	None	None	N
Y/C	0.9589	likely_pathogenic	0.9632	pathogenic	-1.467	Destabilizing	0.995	D	0.889	deleterious	None	None	None	None	N
Y/D	0.9991	likely_pathogenic	0.9991	pathogenic	-2.877	Highly Destabilizing	0.901	D	0.903	deleterious	None	None	None	None	N
Y/E	0.9995	likely_pathogenic	0.9996	pathogenic	-2.63	Highly Destabilizing	0.923	D	0.857	deleterious	None	None	None	None	N
Y/F	0.1347	likely_benign	0.1877	benign	-0.664	Destabilizing	0.008	N	0.451	neutral	None	None	None	None	N
Y/G	0.997	likely_pathogenic	0.9971	pathogenic	-2.462	Highly Destabilizing	0.775	D	0.863	deleterious	None	None	None	None	N
Y/H	0.9858	likely_pathogenic	0.9876	pathogenic	-1.981	Destabilizing	0.983	D	0.734	prob.delet.	None	None	None	None	N
Y/I	0.9276	likely_pathogenic	0.9391	pathogenic	-0.55	Destabilizing	0.858	D	0.815	deleterious	None	None	None	None	N
Y/K	0.9992	likely_pathogenic	0.9994	pathogenic	-1.861	Destabilizing	0.923	D	0.86	deleterious	None	None	None	None	N
Y/L	0.9182	likely_pathogenic	0.916	pathogenic	-0.55	Destabilizing	0.633	D	0.773	deleterious	None	None	None	None	N
Y/M	0.9853	likely_pathogenic	0.9874	pathogenic	-0.656	Destabilizing	0.989	D	0.825	deleterious	None	None	None	None	N
Y/N	0.9946	likely_pathogenic	0.9946	pathogenic	-2.828	Highly Destabilizing	0.901	D	0.89	deleterious	None	None	None	None	N
Y/P	0.9993	likely_pathogenic	0.9995	pathogenic	-1.054	Destabilizing	0.961	D	0.907	deleterious	None	None	None	None	N
Y/Q	0.9992	likely_pathogenic	0.9994	pathogenic	-2.329	Highly Destabilizing	0.961	D	0.819	deleterious	None	None	None	None	N
Y/R	0.9968	likely_pathogenic	0.9975	pathogenic	-2.249	Highly Destabilizing	0.961	D	0.893	deleterious	None	None	None	None	N
Y/S	0.9962	likely_pathogenic	0.9961	pathogenic	-3.071	Highly Destabilizing	0.075	N	0.685	prob.neutral	None	None	None	None	N
Y/T	0.9976	likely_pathogenic	0.9977	pathogenic	-2.674	Highly Destabilizing	0.858	D	0.842	deleterious	None	None	None	None	N
Y/V	0.928	likely_pathogenic	0.9322	pathogenic	-1.054	Destabilizing	0.633	D	0.8	deleterious	None	None	None	None	N
Y/W	0.8473	likely_pathogenic	0.8767	pathogenic	-0.117	Destabilizing	0.996	D	0.739	prob.delet.	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.