TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22128	66607;66608;66609	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
N2AB	20487	61684;61685;61686	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
N2A	19560	58903;58904;58905	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
N2B	13063	39412;39413;39414	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
Novex-1	13188	39787;39788;39789	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
Novex-2	13255	39988;39989;39990	chr2:178581987;178581986;178581985	chr2:179446714;179446713;179446712
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-48
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1744
• 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
F/S	rs2047881254	None	0.991	D	0.745	0.483	0.651281849334	gnomAD-4.0.0	3.18462E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72053E-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
F/A	0.9989	likely_pathogenic	0.9988	pathogenic	-3.013	Highly Destabilizing	0.953	D	0.711	prob.delet.	None	None	None	None	N
F/C	0.9861	likely_pathogenic	0.9824	pathogenic	-1.555	Destabilizing	0.999	D	0.748	deleterious	D	0.554214874	None	None	N
F/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.813	Highly Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
F/E	0.9998	likely_pathogenic	0.9998	pathogenic	-3.577	Highly Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	N
F/G	0.9982	likely_pathogenic	0.9983	pathogenic	-3.461	Highly Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
F/H	0.9964	likely_pathogenic	0.9931	pathogenic	-2.329	Highly Destabilizing	0.986	D	0.699	prob.neutral	None	None	None	None	N
F/I	0.9795	likely_pathogenic	0.9795	pathogenic	-1.516	Destabilizing	0.982	D	0.709	prob.delet.	N	0.503048299	None	None	N
F/K	0.9998	likely_pathogenic	0.9997	pathogenic	-2.38	Highly Destabilizing	0.993	D	0.792	deleterious	None	None	None	None	N
F/L	0.9968	likely_pathogenic	0.9974	pathogenic	-1.516	Destabilizing	0.885	D	0.695	prob.neutral	N	0.493946946	None	None	N
F/M	0.9872	likely_pathogenic	0.9868	pathogenic	-1.067	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
F/N	0.9985	likely_pathogenic	0.9979	pathogenic	-3.066	Highly Destabilizing	0.993	D	0.803	deleterious	None	None	None	None	N
F/P	1.0	likely_pathogenic	1.0	pathogenic	-2.033	Highly Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	N
F/Q	0.9997	likely_pathogenic	0.9995	pathogenic	-2.914	Highly Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
F/R	0.9994	likely_pathogenic	0.9993	pathogenic	-2.082	Highly Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
F/S	0.9988	likely_pathogenic	0.9984	pathogenic	-3.496	Highly Destabilizing	0.991	D	0.745	deleterious	D	0.554214874	None	None	N
F/T	0.9992	likely_pathogenic	0.9991	pathogenic	-3.143	Highly Destabilizing	0.993	D	0.751	deleterious	None	None	None	None	N
F/V	0.9818	likely_pathogenic	0.9819	pathogenic	-2.033	Highly Destabilizing	0.939	D	0.661	neutral	N	0.478837523	None	None	N
F/W	0.9036	likely_pathogenic	0.8815	pathogenic	-0.725	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
F/Y	0.3455	ambiguous	0.3633	ambiguous	-1.169	Destabilizing	0.046	N	0.265	neutral	N	0.481353327	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.