TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7447	22564;22565;22566	chr2:178722448;178722447;178722446	chr2:179587175;179587174;179587173
N2AB	7130	21613;21614;21615	chr2:178722448;178722447;178722446	chr2:179587175;179587174;179587173
N2A	6203	18832;18833;18834	chr2:178722448;178722447;178722446	chr2:179587175;179587174;179587173
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-59
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.808
• Predicted PPI site: I

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
P/S	rs749750693	0.027	0.999	N	0.625	0.46	0.493628743246	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	9.96E-05	0	None	0	None	0	0	0
P/S	rs749750693	0.027	0.999	N	0.625	0.46	0.493628743246	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	2.88018E-04	0	None	0	0	0	0	0
P/S	rs749750693	0.027	0.999	N	0.625	0.46	0.493628743246	gnomAD-4.0.0	2.47938E-06	None	None	None	None	I	None	0	0	None	1.01392E-04	0	None	0	0	8.47781E-07	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
P/A	0.254	likely_benign	0.201	benign	-0.375	Destabilizing	0.987	D	0.645	neutral	N	0.482881626	None	None	I
P/C	0.8981	likely_pathogenic	0.8997	pathogenic	-0.621	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/D	0.6262	likely_pathogenic	0.6338	pathogenic	-0.353	Destabilizing	0.988	D	0.624	neutral	None	None	None	None	I
P/E	0.5636	ambiguous	0.5308	ambiguous	-0.474	Destabilizing	0.95	D	0.632	neutral	None	None	None	None	I
P/F	0.8709	likely_pathogenic	0.8538	pathogenic	-0.685	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
P/G	0.6103	likely_pathogenic	0.633	pathogenic	-0.478	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	I
P/H	0.5468	ambiguous	0.5015	ambiguous	-0.091	Destabilizing	1.0	D	0.655	neutral	D	0.538475065	None	None	I
P/I	0.7653	likely_pathogenic	0.7196	pathogenic	-0.256	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
P/K	0.7078	likely_pathogenic	0.6526	pathogenic	-0.416	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	I
P/L	0.4569	ambiguous	0.3804	ambiguous	-0.256	Destabilizing	1.0	D	0.671	neutral	N	0.499037325	None	None	I
P/M	0.7471	likely_pathogenic	0.6992	pathogenic	-0.401	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
P/N	0.5884	likely_pathogenic	0.6005	pathogenic	-0.153	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	I
P/Q	0.4815	ambiguous	0.4207	ambiguous	-0.396	Destabilizing	0.989	D	0.527	neutral	None	None	None	None	I
P/R	0.5136	ambiguous	0.4373	ambiguous	0.084	Stabilizing	1.0	D	0.659	neutral	N	0.489326861	None	None	I
P/S	0.3504	ambiguous	0.3145	benign	-0.464	Destabilizing	0.999	D	0.625	neutral	N	0.494162253	None	None	I
P/T	0.3553	ambiguous	0.315	benign	-0.488	Destabilizing	0.999	D	0.635	neutral	N	0.482121158	None	None	I
P/V	0.5851	likely_pathogenic	0.5296	ambiguous	-0.263	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	I
P/W	0.9439	likely_pathogenic	0.9415	pathogenic	-0.77	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
P/Y	0.8382	likely_pathogenic	0.8271	pathogenic	-0.47	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I

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.