TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27476	82651;82652;82653	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
N2AB	25835	77728;77729;77730	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
N2A	24908	74947;74948;74949	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
N2B	18411	55456;55457;55458	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
Novex-1	18536	55831;55832;55833	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
Novex-2	18603	56032;56033;56034	chr2:178563706;178563705;178563704	chr2:179428433;179428432;179428431
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: Fn3-88
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.4123
• 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/R	rs2154161598	None	1.0	D	0.917	0.43	0.542764462858	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
P/S	None	None	1.0	D	0.86	0.455	0.474406357249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.5174	ambiguous	0.5886	pathogenic	-2.217	Highly Destabilizing	1.0	D	0.846	deleterious	N	0.501576587	None	None	I
P/C	0.9313	likely_pathogenic	0.9496	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
P/D	0.9984	likely_pathogenic	0.9984	pathogenic	-2.977	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
P/E	0.9912	likely_pathogenic	0.9914	pathogenic	-2.762	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/F	0.9912	likely_pathogenic	0.9934	pathogenic	-1.379	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	I
P/G	0.9694	likely_pathogenic	0.9754	pathogenic	-2.724	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
P/H	0.9923	likely_pathogenic	0.9933	pathogenic	-2.35	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.543407411	None	None	I
P/I	0.6327	likely_pathogenic	0.6942	pathogenic	-0.797	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	I
P/K	0.9932	likely_pathogenic	0.9933	pathogenic	-1.754	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
P/L	0.3712	ambiguous	0.4269	ambiguous	-0.797	Destabilizing	1.0	D	0.901	deleterious	N	0.475949028	None	None	I
P/M	0.841	likely_pathogenic	0.8814	pathogenic	-1.258	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
P/N	0.9955	likely_pathogenic	0.996	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	I
P/Q	0.9812	likely_pathogenic	0.9839	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
P/R	0.9854	likely_pathogenic	0.986	pathogenic	-1.596	Destabilizing	1.0	D	0.917	deleterious	D	0.543407411	None	None	I
P/S	0.9487	likely_pathogenic	0.96	pathogenic	-2.775	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.525049666	None	None	I
P/T	0.7742	likely_pathogenic	0.8198	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.542900432	None	None	I
P/V	0.4212	ambiguous	0.4922	ambiguous	-1.245	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
P/W	0.9981	likely_pathogenic	0.9987	pathogenic	-1.777	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
P/Y	0.9969	likely_pathogenic	0.9977	pathogenic	-1.446	Destabilizing	1.0	D	0.922	deleterious	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.