TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14497	43714;43715;43716	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
N2AB	12856	38791;38792;38793	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
N2A	11929	36010;36011;36012	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
N2B	5432	16519;16520;16521	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
Novex-1	5557	16894;16895;16896	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
Novex-2	5624	17095;17096;17097	chr2:178632405;178632404;178632403	chr2:179497132;179497131;179497130
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-96
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2373
• 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	None	None	1.0	D	0.773	0.611	0.872922419221	gnomAD-4.0.0	1.67021E-06	None	None	None	None	N	None	0	0	None	0	2.82294E-05	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	0.8815	likely_pathogenic	0.904	pathogenic	-1.981	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
L/C	0.9235	likely_pathogenic	0.9185	pathogenic	-1.019	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
L/D	0.9912	likely_pathogenic	0.9938	pathogenic	-1.706	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/E	0.9416	likely_pathogenic	0.958	pathogenic	-1.637	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
L/F	0.6925	likely_pathogenic	0.713	pathogenic	-1.339	Destabilizing	1.0	D	0.663	neutral	D	0.664072499	None	None	N
L/G	0.9645	likely_pathogenic	0.9726	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/H	0.9298	likely_pathogenic	0.9451	pathogenic	-1.493	Destabilizing	1.0	D	0.755	deleterious	D	0.664160344	None	None	N
L/I	0.2552	likely_benign	0.2429	benign	-1.014	Destabilizing	0.999	D	0.513	neutral	D	0.542630577	None	None	N
L/K	0.9106	likely_pathogenic	0.9311	pathogenic	-1.389	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/M	0.3889	ambiguous	0.3872	ambiguous	-0.808	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
L/N	0.9567	likely_pathogenic	0.9669	pathogenic	-1.237	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/P	0.7924	likely_pathogenic	0.8362	pathogenic	-1.311	Destabilizing	1.0	D	0.773	deleterious	D	0.621603911	None	None	N
L/Q	0.872	likely_pathogenic	0.9026	pathogenic	-1.34	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/R	0.8795	likely_pathogenic	0.9082	pathogenic	-0.878	Destabilizing	1.0	D	0.781	deleterious	D	0.664072499	None	None	N
L/S	0.9592	likely_pathogenic	0.9697	pathogenic	-1.795	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/T	0.8654	likely_pathogenic	0.8921	pathogenic	-1.604	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
L/V	0.2875	likely_benign	0.2905	benign	-1.311	Destabilizing	0.999	D	0.55	neutral	D	0.548253452	None	None	N
L/W	0.862	likely_pathogenic	0.8762	pathogenic	-1.442	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
L/Y	0.9297	likely_pathogenic	0.9395	pathogenic	-1.238	Destabilizing	1.0	D	0.705	prob.neutral	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.