TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15447	46564;46565;46566	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
N2AB	13806	41641;41642;41643	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
N2A	12879	38860;38861;38862	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
N2B	6382	19369;19370;19371	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
Novex-1	6507	19744;19745;19746	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
Novex-2	6574	19945;19946;19947	chr2:178620078;178620077;178620076	chr2:179484805;179484804;179484803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-106
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.058
• 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/F	None	None	1.0	D	0.81	0.724	0.909987953017	gnomAD-4.0.0	1.59565E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43666E-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
L/A	0.9856	likely_pathogenic	0.9915	pathogenic	-2.009	Highly Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
L/C	0.9596	likely_pathogenic	0.9816	pathogenic	-1.258	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-2.636	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/E	0.999	likely_pathogenic	0.9994	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/F	0.9035	likely_pathogenic	0.9381	pathogenic	-1.286	Destabilizing	1.0	D	0.81	deleterious	D	0.686842367	None	None	N
L/G	0.9961	likely_pathogenic	0.9978	pathogenic	-2.444	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/H	0.9978	likely_pathogenic	0.9987	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.738461817	None	None	N
L/I	0.6614	likely_pathogenic	0.6808	pathogenic	-0.683	Destabilizing	0.999	D	0.617	neutral	D	0.663915002	None	None	N
L/K	0.9975	likely_pathogenic	0.9985	pathogenic	-1.673	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/M	0.5432	ambiguous	0.7078	pathogenic	-0.982	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/N	0.9989	likely_pathogenic	0.9993	pathogenic	-2.38	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/P	0.9997	likely_pathogenic	0.9998	pathogenic	-1.122	Destabilizing	1.0	D	0.889	deleterious	D	0.705668374	None	None	N
L/Q	0.9957	likely_pathogenic	0.998	pathogenic	-1.968	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/R	0.9952	likely_pathogenic	0.9966	pathogenic	-2.028	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.738461817	None	None	N
L/S	0.9992	likely_pathogenic	0.9996	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/T	0.9968	likely_pathogenic	0.9981	pathogenic	-2.219	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
L/V	0.7639	likely_pathogenic	0.8043	pathogenic	-1.122	Destabilizing	0.999	D	0.615	neutral	D	0.686842367	None	None	N
L/W	0.9954	likely_pathogenic	0.9973	pathogenic	-1.489	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/Y	0.9936	likely_pathogenic	0.996	pathogenic	-1.445	Destabilizing	1.0	D	0.855	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.