TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22079	66460;66461;66462	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
N2AB	20438	61537;61538;61539	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
N2A	19511	58756;58757;58758	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
N2B	13014	39265;39266;39267	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
Novex-1	13139	39640;39641;39642	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
Novex-2	13206	39841;39842;39843	chr2:178582134;178582133;178582132	chr2:179446861;179446860;179446859
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: Fn3-48
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1167
• 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	rs1379026615	None	1.0	D	0.91	0.601	0.733105195128	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1379026615	None	1.0	D	0.91	0.601	0.733105195128	gnomAD-4.0.0	6.41453E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19724E-05	0	0
P/S	None	None	1.0	N	0.873	0.489	0.459729313489	gnomAD-4.0.0	6.84686E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99656E-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	0.906	likely_pathogenic	0.7628	pathogenic	-1.814	Destabilizing	1.0	D	0.835	deleterious	N	0.511880752	None	None	N
P/C	0.9918	likely_pathogenic	0.9765	pathogenic	-1.018	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/D	0.9987	likely_pathogenic	0.9976	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9941	pathogenic	-2.08	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9989	pathogenic	-1.555	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
P/G	0.9917	likely_pathogenic	0.9826	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/H	0.9969	likely_pathogenic	0.9918	pathogenic	-1.847	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/I	0.9951	likely_pathogenic	0.9853	pathogenic	-0.981	Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/K	0.9984	likely_pathogenic	0.9963	pathogenic	-1.501	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
P/L	0.9809	likely_pathogenic	0.9454	pathogenic	-0.981	Destabilizing	1.0	D	0.91	deleterious	D	0.54321419	None	None	N
P/M	0.997	likely_pathogenic	0.9916	pathogenic	-0.574	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/N	0.9988	likely_pathogenic	0.9972	pathogenic	-1.219	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
P/Q	0.9967	likely_pathogenic	0.9896	pathogenic	-1.415	Destabilizing	1.0	D	0.868	deleterious	D	0.556344922	None	None	N
P/R	0.995	likely_pathogenic	0.9879	pathogenic	-0.961	Destabilizing	1.0	D	0.895	deleterious	D	0.537987178	None	None	N
P/S	0.9857	likely_pathogenic	0.9529	pathogenic	-1.64	Destabilizing	1.0	D	0.873	deleterious	N	0.500270957	None	None	N
P/T	0.9797	likely_pathogenic	0.9394	pathogenic	-1.542	Destabilizing	1.0	D	0.877	deleterious	D	0.529086408	None	None	N
P/V	0.9804	likely_pathogenic	0.9427	pathogenic	-1.228	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9996	pathogenic	-1.796	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9988	pathogenic	-1.539	Destabilizing	1.0	D	0.904	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.