TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27837	83734;83735;83736	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
N2AB	26196	78811;78812;78813	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
N2A	25269	76030;76031;76032	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
N2B	18772	56539;56540;56541	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
Novex-1	18897	56914;56915;56916	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
Novex-2	18964	57115;57116;57117	chr2:178562623;178562622;178562621	chr2:179427350;179427349;179427348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-90
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1952
• 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
Y/C	rs1324677540	-1.237	0.992	N	0.709	0.333	0.735914652579	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
Y/C	rs1324677540	-1.237	0.992	N	0.709	0.333	0.735914652579	gnomAD-4.0.0	1.60393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87135E-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
Y/A	0.6038	likely_pathogenic	0.5465	ambiguous	-2.91	Highly Destabilizing	0.668	D	0.618	neutral	None	None	None	None	N
Y/C	0.1573	likely_benign	0.1466	benign	-1.344	Destabilizing	0.992	D	0.709	prob.delet.	N	0.478027829	None	None	N
Y/D	0.6935	likely_pathogenic	0.6712	pathogenic	-2.471	Highly Destabilizing	0.915	D	0.731	prob.delet.	D	0.5225779	None	None	N
Y/E	0.8793	likely_pathogenic	0.8571	pathogenic	-2.293	Highly Destabilizing	0.876	D	0.652	neutral	None	None	None	None	N
Y/F	0.083	likely_benign	0.0738	benign	-1.058	Destabilizing	0.001	N	0.473	neutral	N	0.456219622	None	None	N
Y/G	0.6261	likely_pathogenic	0.5909	pathogenic	-3.284	Highly Destabilizing	0.935	D	0.688	prob.neutral	None	None	None	None	N
Y/H	0.2227	likely_benign	0.1979	benign	-1.717	Destabilizing	0.003	N	0.475	neutral	N	0.505434934	None	None	N
Y/I	0.487	ambiguous	0.4124	ambiguous	-1.683	Destabilizing	0.121	N	0.623	neutral	None	None	None	None	N
Y/K	0.7971	likely_pathogenic	0.7553	pathogenic	-1.544	Destabilizing	0.461	N	0.695	prob.neutral	None	None	None	None	N
Y/L	0.4238	ambiguous	0.3858	ambiguous	-1.683	Destabilizing	0.038	N	0.571	neutral	None	None	None	None	N
Y/M	0.6595	likely_pathogenic	0.5757	pathogenic	-1.386	Destabilizing	0.942	D	0.657	neutral	None	None	None	None	N
Y/N	0.3622	ambiguous	0.3088	benign	-2.083	Highly Destabilizing	0.842	D	0.701	prob.neutral	N	0.502258556	None	None	N
Y/P	0.9827	likely_pathogenic	0.9843	pathogenic	-2.103	Highly Destabilizing	0.978	D	0.757	deleterious	None	None	None	None	N
Y/Q	0.6506	likely_pathogenic	0.6017	pathogenic	-1.942	Destabilizing	0.812	D	0.668	neutral	None	None	None	None	N
Y/R	0.5872	likely_pathogenic	0.5693	pathogenic	-1.225	Destabilizing	0.746	D	0.697	prob.neutral	None	None	None	None	N
Y/S	0.2913	likely_benign	0.2693	benign	-2.573	Highly Destabilizing	0.915	D	0.653	neutral	N	0.495889944	None	None	N
Y/T	0.5226	ambiguous	0.4493	ambiguous	-2.29	Highly Destabilizing	0.935	D	0.689	prob.neutral	None	None	None	None	N
Y/V	0.3977	ambiguous	0.3361	benign	-2.103	Highly Destabilizing	0.502	D	0.595	neutral	None	None	None	None	N
Y/W	0.4779	ambiguous	0.4914	ambiguous	-0.317	Destabilizing	0.968	D	0.642	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.