TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18089	54490;54491;54492	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
N2AB	16448	49567;49568;49569	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
N2A	15521	46786;46787;46788	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
N2B	9024	27295;27296;27297	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
Novex-1	9149	27670;27671;27672	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
Novex-2	9216	27871;27872;27873	chr2:178604824;178604823;178604822	chr2:179469551;179469550;179469549
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-19
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1436
• 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/S	None	None	1.0	N	0.837	0.642	0.367803931526	gnomAD-4.0.0	1.59408E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43439E-05	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	0.9187	likely_pathogenic	0.9201	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.806	deleterious	N	0.501676536	None	None	N
P/C	0.9915	likely_pathogenic	0.9929	pathogenic	-1.611	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
P/D	0.9989	likely_pathogenic	0.9989	pathogenic	-2.799	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/E	0.9982	likely_pathogenic	0.9982	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/F	0.9995	likely_pathogenic	0.9996	pathogenic	-1.428	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/G	0.9927	likely_pathogenic	0.9919	pathogenic	-2.515	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/H	0.9975	likely_pathogenic	0.9973	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.540544845	None	None	N
P/I	0.9953	likely_pathogenic	0.9965	pathogenic	-0.896	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9992	pathogenic	-1.833	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
P/L	0.979	likely_pathogenic	0.9833	pathogenic	-0.896	Destabilizing	1.0	D	0.88	deleterious	N	0.520666163	None	None	N
P/M	0.9968	likely_pathogenic	0.9977	pathogenic	-0.765	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/N	0.9988	likely_pathogenic	0.9988	pathogenic	-1.914	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
P/Q	0.9974	likely_pathogenic	0.9973	pathogenic	-1.938	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/R	0.9972	likely_pathogenic	0.9969	pathogenic	-1.428	Destabilizing	1.0	D	0.871	deleterious	N	0.504082845	None	None	N
P/S	0.9858	likely_pathogenic	0.9845	pathogenic	-2.43	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.490725077	None	None	N
P/T	0.9836	likely_pathogenic	0.9847	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.521680121	None	None	N
P/V	0.9828	likely_pathogenic	0.9864	pathogenic	-1.261	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9998	pathogenic	-1.887	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9996	pathogenic	-1.568	Destabilizing	1.0	D	0.87	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.