TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32777	98554;98555;98556	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
N2AB	31136	93631;93632;93633	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
N2A	30209	90850;90851;90852	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
N2B	23712	71359;71360;71361	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
Novex-1	23837	71734;71735;71736	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
Novex-2	23904	71935;71936;71937	chr2:178539736;178539735;178539734	chr2:179404463;179404462;179404461
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-155
• Domain position: 70
• Structural Position: 158
• Q(SASA): 0.1214
• 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/R	rs1553510213	None	1.0	N	0.8	0.601	0.815153439622	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.7039	likely_pathogenic	0.7716	pathogenic	-2.546	Highly Destabilizing	0.997	D	0.615	neutral	None	None	None	None	I
L/C	0.8464	likely_pathogenic	0.8749	pathogenic	-1.6	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
L/D	0.9994	likely_pathogenic	0.9996	pathogenic	-2.836	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
L/E	0.9951	likely_pathogenic	0.9966	pathogenic	-2.721	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
L/F	0.8242	likely_pathogenic	0.8506	pathogenic	-1.643	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
L/G	0.9737	likely_pathogenic	0.9814	pathogenic	-2.988	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	I
L/H	0.9937	likely_pathogenic	0.9961	pathogenic	-2.411	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
L/I	0.2232	likely_benign	0.2511	benign	-1.304	Destabilizing	0.994	D	0.568	neutral	None	None	None	None	I
L/K	0.995	likely_pathogenic	0.9965	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
L/M	0.3314	likely_benign	0.3651	ambiguous	-0.976	Destabilizing	0.999	D	0.773	deleterious	N	0.512875619	None	None	I
L/N	0.9956	likely_pathogenic	0.9969	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	I
L/P	0.9963	likely_pathogenic	0.9974	pathogenic	-1.697	Destabilizing	1.0	D	0.81	deleterious	N	0.501608219	None	None	I
L/Q	0.9801	likely_pathogenic	0.9865	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.802	deleterious	N	0.513129108	None	None	I
L/R	0.9862	likely_pathogenic	0.9905	pathogenic	-1.519	Destabilizing	1.0	D	0.8	deleterious	N	0.513129108	None	None	I
L/S	0.9697	likely_pathogenic	0.9811	pathogenic	-2.668	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
L/T	0.8732	likely_pathogenic	0.9184	pathogenic	-2.441	Highly Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
L/V	0.2162	likely_benign	0.2681	benign	-1.697	Destabilizing	0.767	D	0.368	neutral	N	0.471194648	None	None	I
L/W	0.9834	likely_pathogenic	0.9887	pathogenic	-1.991	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
L/Y	0.9877	likely_pathogenic	0.9911	pathogenic	-1.782	Destabilizing	1.0	D	0.795	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.