TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32055	96388;96389;96390	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
N2AB	30414	91465;91466;91467	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
N2A	29487	88684;88685;88686	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
N2B	22990	69193;69194;69195	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
Novex-1	23115	69568;69569;69570	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
Novex-2	23182	69769;69770;69771	chr2:178543981;178543980;178543979	chr2:179408708;179408707;179408706
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: Ig-153
• Domain position: 39
• Structural Position: 58
• Q(SASA): 0.2513
• 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/F	None	None	1.0	N	0.721	0.618	0.770224981595	gnomAD-4.0.0	1.59142E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-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	0.7588	likely_pathogenic	0.719	pathogenic	-2.28	Highly Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
L/C	0.911	likely_pathogenic	0.898	pathogenic	-1.897	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
L/D	0.9853	likely_pathogenic	0.9807	pathogenic	-1.581	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
L/E	0.9553	likely_pathogenic	0.939	pathogenic	-1.367	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
L/F	0.4649	ambiguous	0.4199	ambiguous	-1.345	Destabilizing	1.0	D	0.721	prob.delet.	N	0.504403966	None	None	I
L/G	0.9548	likely_pathogenic	0.9427	pathogenic	-2.815	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
L/H	0.9241	likely_pathogenic	0.8952	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.828	deleterious	D	0.561211946	None	None	I
L/I	0.1318	likely_benign	0.1267	benign	-0.76	Destabilizing	0.999	D	0.485	neutral	N	0.486577893	None	None	I
L/K	0.9527	likely_pathogenic	0.9316	pathogenic	-1.695	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
L/M	0.2405	likely_benign	0.223	benign	-0.866	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
L/N	0.9446	likely_pathogenic	0.9294	pathogenic	-1.949	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
L/P	0.6853	likely_pathogenic	0.6176	pathogenic	-1.244	Destabilizing	1.0	D	0.833	deleterious	D	0.554375091	None	None	I
L/Q	0.9104	likely_pathogenic	0.8744	pathogenic	-1.758	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
L/R	0.9262	likely_pathogenic	0.8932	pathogenic	-1.525	Destabilizing	1.0	D	0.833	deleterious	D	0.554375091	None	None	I
L/S	0.9269	likely_pathogenic	0.9013	pathogenic	-2.803	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
L/T	0.67	likely_pathogenic	0.6236	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
L/V	0.1732	likely_benign	0.1669	benign	-1.244	Destabilizing	0.999	D	0.486	neutral	N	0.495993267	None	None	I
L/W	0.8602	likely_pathogenic	0.822	pathogenic	-1.529	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
L/Y	0.8905	likely_pathogenic	0.8656	pathogenic	-1.278	Destabilizing	1.0	D	0.82	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.