TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4709	14350;14351;14352	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
N2AB	4392	13399;13400;13401	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
N2A	3465	10618;10619;10620	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
N2B	4346	13261;13262;13263	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
Novex-1	4471	13636;13637;13638	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
Novex-2	4538	13837;13838;13839	chr2:178738328;178738327;178738326	chr2:179603055;179603054;179603053
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-30
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.3299
• 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/P	rs756566095	-1.035	0.971	D	0.72	0.548	0.731923157262	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
L/P	rs756566095	-1.035	0.971	D	0.72	0.548	0.731923157262	gnomAD-4.0.0	1.59303E-06	None	None	None	None	I	None	0	0	None	0	2.78149E-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	0.2033	likely_benign	0.2637	benign	-1.474	Destabilizing	0.754	D	0.44	neutral	None	None	None	None	I
L/C	0.5672	likely_pathogenic	0.6248	pathogenic	-0.909	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	I
L/D	0.8175	likely_pathogenic	0.8693	pathogenic	-0.392	Destabilizing	0.956	D	0.711	prob.delet.	None	None	None	None	I
L/E	0.2663	likely_benign	0.3527	ambiguous	-0.325	Destabilizing	0.754	D	0.624	neutral	None	None	None	None	I
L/F	0.2419	likely_benign	0.2657	benign	-0.818	Destabilizing	0.993	D	0.56	neutral	None	None	None	None	I
L/G	0.6314	likely_pathogenic	0.7431	pathogenic	-1.855	Destabilizing	0.956	D	0.699	prob.neutral	None	None	None	None	I
L/H	0.3136	likely_benign	0.3741	ambiguous	-1.084	Destabilizing	0.994	D	0.698	prob.neutral	None	None	None	None	I
L/I	0.0875	likely_benign	0.085	benign	-0.485	Destabilizing	0.926	D	0.406	neutral	None	None	None	None	I
L/K	0.225	likely_benign	0.2733	benign	-0.816	Destabilizing	0.915	D	0.585	neutral	None	None	None	None	I
L/M	0.0986	likely_benign	0.1064	benign	-0.501	Destabilizing	0.971	D	0.581	neutral	N	0.50672811	None	None	I
L/N	0.5502	ambiguous	0.623	pathogenic	-0.721	Destabilizing	0.956	D	0.718	prob.delet.	None	None	None	None	I
L/P	0.9263	likely_pathogenic	0.9523	pathogenic	-0.784	Destabilizing	0.971	D	0.72	prob.delet.	D	0.545039717	None	None	I
L/Q	0.0938	likely_benign	0.1374	benign	-0.754	Destabilizing	0.058	N	0.341	neutral	N	0.494212521	None	None	I
L/R	0.1759	likely_benign	0.2301	benign	-0.465	Destabilizing	0.89	D	0.664	neutral	N	0.518002921	None	None	I
L/S	0.277	likely_benign	0.3684	ambiguous	-1.466	Destabilizing	0.915	D	0.585	neutral	None	None	None	None	I
L/T	0.1611	likely_benign	0.1968	benign	-1.265	Destabilizing	0.956	D	0.597	neutral	None	None	None	None	I
L/V	0.0715	likely_benign	0.0749	benign	-0.784	Destabilizing	0.822	D	0.353	neutral	N	0.458740583	None	None	I
L/W	0.4041	ambiguous	0.4631	ambiguous	-0.929	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	I
L/Y	0.5378	ambiguous	0.5695	pathogenic	-0.66	Destabilizing	0.978	D	0.657	neutral	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.