TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9019	27280;27281;27282	chr2:178712970;178712969;178712968	chr2:179577697;179577696;179577695
N2AB	8702	26329;26330;26331	chr2:178712970;178712969;178712968	chr2:179577697;179577696;179577695
N2A	7775	23548;23549;23550	chr2:178712970;178712969;178712968	chr2:179577697;179577696;179577695
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-76
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1801
• 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
P/L	None	None	0.998	D	0.885	0.76	0.907006725545	gnomAD-4.0.0	1.37006E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80058E-06	0	0
P/R	None	None	0.999	D	0.905	0.815	0.85697642895	gnomAD-4.0.0	6.85028E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00289E-07	0	0
P/S	rs2076880929	None	0.995	D	0.847	0.824	0.645952563013	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs2076880929	None	0.995	D	0.847	0.824	0.645952563013	gnomAD-4.0.0	2.56768E-06	None	None	None	None	N	None	3.38467E-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
P/A	0.5745	likely_pathogenic	0.6545	pathogenic	-1.609	Destabilizing	0.619	D	0.699	prob.neutral	D	0.605404597	None	None	N
P/C	0.9728	likely_pathogenic	0.9807	pathogenic	-1.305	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/D	0.9986	likely_pathogenic	0.9988	pathogenic	-0.995	Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
P/E	0.9942	likely_pathogenic	0.9953	pathogenic	-0.901	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	N
P/F	0.9938	likely_pathogenic	0.9962	pathogenic	-1.044	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/G	0.9813	likely_pathogenic	0.9868	pathogenic	-2.025	Highly Destabilizing	0.988	D	0.854	deleterious	None	None	None	None	N
P/H	0.9907	likely_pathogenic	0.9929	pathogenic	-1.527	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/I	0.8794	likely_pathogenic	0.9153	pathogenic	-0.526	Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
P/K	0.9959	likely_pathogenic	0.9971	pathogenic	-1.113	Destabilizing	0.998	D	0.905	deleterious	None	None	None	None	N
P/L	0.7558	likely_pathogenic	0.8262	pathogenic	-0.526	Destabilizing	0.998	D	0.885	deleterious	D	0.654098453	None	None	N
P/M	0.9692	likely_pathogenic	0.9793	pathogenic	-0.61	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/N	0.9971	likely_pathogenic	0.9978	pathogenic	-1.067	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/Q	0.9863	likely_pathogenic	0.9894	pathogenic	-1.08	Destabilizing	1.0	D	0.897	deleterious	D	0.654300257	None	None	N
P/R	0.9842	likely_pathogenic	0.9882	pathogenic	-0.842	Destabilizing	0.999	D	0.905	deleterious	D	0.654300257	None	None	N
P/S	0.9402	likely_pathogenic	0.9567	pathogenic	-1.801	Destabilizing	0.995	D	0.847	deleterious	D	0.637877288	None	None	N
P/T	0.9109	likely_pathogenic	0.9361	pathogenic	-1.569	Destabilizing	0.998	D	0.893	deleterious	D	0.638079092	None	None	N
P/V	0.7558	likely_pathogenic	0.8214	pathogenic	-0.853	Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
P/W	0.9989	likely_pathogenic	0.9992	pathogenic	-1.269	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/Y	0.9967	likely_pathogenic	0.9978	pathogenic	-0.929	Destabilizing	1.0	D	0.9	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.