TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7287	22084;22085;22086	chr2:178723148;178723147;178723146	chr2:179587875;179587874;179587873
N2AB	6970	21133;21134;21135	chr2:178723148;178723147;178723146	chr2:179587875;179587874;179587873
N2A	6043	18352;18353;18354	chr2:178723148;178723147;178723146	chr2:179587875;179587874;179587873
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-57
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0717
• 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/V	rs754054875	-1.544	0.998	D	0.701	0.592	0.737275244558	gnomAD-2.1.1	7.15E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
L/V	rs754054875	-1.544	0.998	D	0.701	0.592	0.737275244558	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs754054875	-1.544	0.998	D	0.701	0.592	0.737275244558	gnomAD-4.0.0	3.09914E-06	None	None	None	None	N	None	6.67824E-05	0	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	0.9143	likely_pathogenic	0.9018	pathogenic	-2.792	Highly Destabilizing	0.997	D	0.774	deleterious	None	None	None	None	N
L/C	0.9323	likely_pathogenic	0.9213	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.719	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/E	0.9971	likely_pathogenic	0.9968	pathogenic	-3.408	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
L/F	0.6175	likely_pathogenic	0.6114	pathogenic	-1.734	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/G	0.9901	likely_pathogenic	0.9889	pathogenic	-3.377	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/H	0.992	likely_pathogenic	0.9904	pathogenic	-3.065	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
L/I	0.2923	likely_benign	0.2372	benign	-1.026	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
L/K	0.9945	likely_pathogenic	0.9933	pathogenic	-2.345	Highly Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
L/M	0.3552	ambiguous	0.3581	ambiguous	-1.149	Destabilizing	1.0	D	0.763	deleterious	D	0.553970244	None	None	N
L/N	0.9983	likely_pathogenic	0.9981	pathogenic	-3.056	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/P	0.9977	likely_pathogenic	0.9971	pathogenic	-1.606	Destabilizing	1.0	D	0.905	deleterious	D	0.566847487	None	None	N
L/Q	0.9853	likely_pathogenic	0.9827	pathogenic	-2.739	Highly Destabilizing	0.981	D	0.676	prob.neutral	D	0.566847487	None	None	N
L/R	0.9849	likely_pathogenic	0.9813	pathogenic	-2.318	Highly Destabilizing	0.999	D	0.891	deleterious	D	0.578368376	None	None	N
L/S	0.9916	likely_pathogenic	0.991	pathogenic	-3.579	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
L/T	0.9649	likely_pathogenic	0.9577	pathogenic	-3.11	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/V	0.3353	likely_benign	0.2686	benign	-1.606	Destabilizing	0.998	D	0.701	prob.neutral	D	0.546968805	None	None	N
L/W	0.9537	likely_pathogenic	0.9475	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/Y	0.9711	likely_pathogenic	0.9683	pathogenic	-1.956	Destabilizing	1.0	D	0.843	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.