TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8128	24607;24608;24609	chr2:178718818;178718817;178718816	chr2:179583545;179583544;179583543
N2AB	7811	23656;23657;23658	chr2:178718818;178718817;178718816	chr2:179583545;179583544;179583543
N2A	6884	20875;20876;20877	chr2:178718818;178718817;178718816	chr2:179583545;179583544;179583543
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-66
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.6297
• 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
L/V	None	None	0.001	N	0.33	0.064	0.247322355667	gnomAD-4.0.0	1.59127E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85837E-06	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
L/A	0.2109	likely_benign	0.2007	benign	-0.934	Destabilizing	0.241	N	0.548	neutral	None	None	None	None	I
L/C	0.5415	ambiguous	0.5237	ambiguous	-0.803	Destabilizing	0.944	D	0.611	neutral	None	None	None	None	I
L/D	0.693	likely_pathogenic	0.6786	pathogenic	-0.01	Destabilizing	0.818	D	0.685	prob.neutral	None	None	None	None	I
L/E	0.303	likely_benign	0.2968	benign	-0.051	Destabilizing	0.69	D	0.676	prob.neutral	None	None	None	None	I
L/F	0.1191	likely_benign	0.1136	benign	-0.694	Destabilizing	0.005	N	0.291	neutral	None	None	None	None	I
L/G	0.5155	ambiguous	0.4973	ambiguous	-1.177	Destabilizing	0.818	D	0.666	neutral	None	None	None	None	I
L/H	0.2004	likely_benign	0.2053	benign	-0.521	Destabilizing	0.981	D	0.658	neutral	None	None	None	None	I
L/I	0.0922	likely_benign	0.088	benign	-0.386	Destabilizing	0.002	N	0.294	neutral	None	None	None	None	I
L/K	0.235	likely_benign	0.2303	benign	-0.509	Destabilizing	0.019	N	0.459	neutral	None	None	None	None	I
L/M	0.1015	likely_benign	0.0971	benign	-0.422	Destabilizing	0.627	D	0.611	neutral	N	0.512533224	None	None	I
L/N	0.4395	ambiguous	0.4234	ambiguous	-0.32	Destabilizing	0.818	D	0.683	prob.neutral	None	None	None	None	I
L/P	0.5412	ambiguous	0.5593	ambiguous	-0.534	Destabilizing	0.912	D	0.685	prob.neutral	N	0.493036617	None	None	I
L/Q	0.1319	likely_benign	0.1361	benign	-0.48	Destabilizing	0.627	D	0.692	prob.neutral	D	0.533846191	None	None	I
L/R	0.1568	likely_benign	0.159	benign	-0.068	Destabilizing	0.457	N	0.695	prob.neutral	N	0.495390021	None	None	I
L/S	0.2224	likely_benign	0.2157	benign	-0.918	Destabilizing	0.69	D	0.678	prob.neutral	None	None	None	None	I
L/T	0.1723	likely_benign	0.1628	benign	-0.84	Destabilizing	0.388	N	0.614	neutral	None	None	None	None	I
L/V	0.0843	likely_benign	0.0826	benign	-0.534	Destabilizing	0.001	N	0.33	neutral	N	0.505792798	None	None	I
L/W	0.2139	likely_benign	0.2112	benign	-0.724	Destabilizing	0.01	N	0.551	neutral	None	None	None	None	I
L/Y	0.3643	ambiguous	0.3505	ambiguous	-0.466	Destabilizing	0.527	D	0.638	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.