TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18749	56470;56471;56472	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
N2AB	17108	51547;51548;51549	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
N2A	16181	48766;48767;48768	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
N2B	9684	29275;29276;29277	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
Novex-1	9809	29650;29651;29652	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
Novex-2	9876	29851;29852;29853	chr2:178599656;178599655;178599654	chr2:179464383;179464382;179464381
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-116
• Domain position: 62
• Structural Position: 138
• Q(SASA): 0.0747
• 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	rs2052744702	None	0.997	D	0.895	0.85	0.902597205664	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9204	likely_pathogenic	0.9137	pathogenic	-2.803	Highly Destabilizing	0.991	D	0.76	deleterious	None	None	None	None	N
L/C	0.9333	likely_pathogenic	0.9218	pathogenic	-2.213	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9994	pathogenic	-3.641	Highly Destabilizing	0.999	D	0.921	deleterious	None	None	None	None	N
L/E	0.9967	likely_pathogenic	0.9959	pathogenic	-3.317	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/F	0.508	ambiguous	0.4553	ambiguous	-1.758	Destabilizing	0.235	N	0.46	neutral	N	0.512152647	None	None	N
L/G	0.9932	likely_pathogenic	0.9914	pathogenic	-3.406	Highly Destabilizing	0.998	D	0.899	deleterious	None	None	None	None	N
L/H	0.9885	likely_pathogenic	0.9858	pathogenic	-3.143	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
L/I	0.1574	likely_benign	0.145	benign	-0.977	Destabilizing	0.955	D	0.66	neutral	D	0.522659578	None	None	N
L/K	0.9928	likely_pathogenic	0.9913	pathogenic	-2.35	Highly Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
L/M	0.2972	likely_benign	0.2574	benign	-1.176	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
L/N	0.9972	likely_pathogenic	0.9964	pathogenic	-3.093	Highly Destabilizing	0.999	D	0.926	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9949	pathogenic	-1.578	Destabilizing	0.999	D	0.925	deleterious	None	None	None	None	N
L/Q	0.9871	likely_pathogenic	0.9837	pathogenic	-2.726	Highly Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
L/R	0.9843	likely_pathogenic	0.9816	pathogenic	-2.429	Highly Destabilizing	0.999	D	0.912	deleterious	None	None	None	None	N
L/S	0.9931	likely_pathogenic	0.9915	pathogenic	-3.631	Highly Destabilizing	0.997	D	0.895	deleterious	D	0.563555804	None	None	N
L/T	0.9657	likely_pathogenic	0.9554	pathogenic	-3.136	Highly Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	N
L/V	0.19	likely_benign	0.1809	benign	-1.578	Destabilizing	0.977	D	0.675	neutral	N	0.509443622	None	None	N
L/W	0.9352	likely_pathogenic	0.9175	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/Y	0.9415	likely_pathogenic	0.9247	pathogenic	-1.959	Destabilizing	0.99	D	0.848	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.