TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25291	76096;76097;76098	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
N2AB	23650	71173;71174;71175	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
N2A	22723	68392;68393;68394	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
N2B	16226	48901;48902;48903	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
Novex-1	16351	49276;49277;49278	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
Novex-2	16418	49477;49478;49479	chr2:178570261;178570260;178570259	chr2:179434988;179434987;179434986
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-71
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.0834
• 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/P	rs1559388448	None	0.994	D	0.851	0.547	0.82834384376	gnomAD-4.0.0	2.05307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69871E-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	0.442	ambiguous	0.4489	ambiguous	-2.275	Highly Destabilizing	0.938	D	0.615	neutral	None	None	None	None	N
L/C	0.5559	ambiguous	0.5924	pathogenic	-1.465	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/D	0.9824	likely_pathogenic	0.9829	pathogenic	-2.226	Highly Destabilizing	0.991	D	0.844	deleterious	None	None	None	None	N
L/E	0.8207	likely_pathogenic	0.8327	pathogenic	-2.094	Highly Destabilizing	0.991	D	0.818	deleterious	None	None	None	None	N
L/F	0.5589	ambiguous	0.5861	pathogenic	-1.367	Destabilizing	0.994	D	0.745	deleterious	D	0.541378809	None	None	N
L/G	0.8562	likely_pathogenic	0.8736	pathogenic	-2.734	Highly Destabilizing	0.991	D	0.808	deleterious	None	None	None	None	N
L/H	0.7643	likely_pathogenic	0.7726	pathogenic	-2.106	Highly Destabilizing	0.999	D	0.849	deleterious	D	0.541885788	None	None	N
L/I	0.1786	likely_benign	0.1525	benign	-1.0	Destabilizing	0.958	D	0.611	neutral	N	0.492800035	None	None	N
L/K	0.668	likely_pathogenic	0.7078	pathogenic	-1.763	Destabilizing	0.991	D	0.794	deleterious	None	None	None	None	N
L/M	0.2154	likely_benign	0.2155	benign	-0.857	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
L/N	0.8969	likely_pathogenic	0.9024	pathogenic	-1.807	Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
L/P	0.9876	likely_pathogenic	0.9898	pathogenic	-1.401	Destabilizing	0.994	D	0.851	deleterious	D	0.530275993	None	None	N
L/Q	0.4557	ambiguous	0.4834	ambiguous	-1.817	Destabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
L/R	0.4911	ambiguous	0.5415	ambiguous	-1.317	Destabilizing	0.988	D	0.821	deleterious	D	0.541378809	None	None	N
L/S	0.6925	likely_pathogenic	0.6931	pathogenic	-2.471	Highly Destabilizing	0.982	D	0.731	prob.delet.	None	None	None	None	N
L/T	0.4503	ambiguous	0.4367	ambiguous	-2.214	Highly Destabilizing	0.18	N	0.457	neutral	None	None	None	None	N
L/V	0.1444	likely_benign	0.1359	benign	-1.401	Destabilizing	0.919	D	0.613	neutral	D	0.531790108	None	None	N
L/W	0.8185	likely_pathogenic	0.833	pathogenic	-1.656	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/Y	0.8475	likely_pathogenic	0.8664	pathogenic	-1.396	Destabilizing	0.998	D	0.811	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.