TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6568	19927;19928;19929	chr2:178728122;178728121;178728120	chr2:179592849;179592848;179592847
N2AB	6251	18976;18977;18978	chr2:178728122;178728121;178728120	chr2:179592849;179592848;179592847
N2A	5324	16195;16196;16197	chr2:178728122;178728121;178728120	chr2:179592849;179592848;179592847
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: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-49
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0977
• 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
L/S	rs1297518586	None	1.0	D	0.912	0.642	0.860891292117	gnomAD-4.0.0	1.69465E-06	None	None	None	None	N	None	0	2.57559E-05	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
L/A	0.9177	likely_pathogenic	0.9205	pathogenic	-2.929	Highly Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
L/C	0.9089	likely_pathogenic	0.9187	pathogenic	-2.457	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
L/D	0.9991	likely_pathogenic	0.9993	pathogenic	-3.615	Highly Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
L/E	0.9937	likely_pathogenic	0.9951	pathogenic	-3.372	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/F	0.5286	ambiguous	0.622	pathogenic	-1.831	Destabilizing	0.999	D	0.831	deleterious	D	0.52523852	None	None	N
L/G	0.9885	likely_pathogenic	0.9898	pathogenic	-3.502	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
L/H	0.9806	likely_pathogenic	0.9863	pathogenic	-3.001	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/I	0.1328	likely_benign	0.166	benign	-1.247	Destabilizing	0.884	D	0.345	neutral	N	0.494457606	None	None	N
L/K	0.9917	likely_pathogenic	0.9934	pathogenic	-2.413	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/M	0.3358	likely_benign	0.3641	ambiguous	-1.267	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/N	0.9943	likely_pathogenic	0.9955	pathogenic	-2.877	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/P	0.9942	likely_pathogenic	0.9956	pathogenic	-1.792	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/Q	0.9707	likely_pathogenic	0.9772	pathogenic	-2.711	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
L/R	0.9775	likely_pathogenic	0.9822	pathogenic	-2.084	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/S	0.9836	likely_pathogenic	0.9866	pathogenic	-3.548	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.556131112	None	None	N
L/T	0.942	likely_pathogenic	0.9522	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/V	0.1509	likely_benign	0.1859	benign	-1.792	Destabilizing	0.981	D	0.643	neutral	N	0.468814798	None	None	N
L/W	0.936	likely_pathogenic	0.9559	pathogenic	-2.297	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/Y	0.9566	likely_pathogenic	0.9674	pathogenic	-2.056	Highly Destabilizing	1.0	D	0.881	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.