TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29769	89530;89531;89532	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
N2AB	28128	84607;84608;84609	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
N2A	27201	81826;81827;81828	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
N2B	20704	62335;62336;62337	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
Novex-1	20829	62710;62711;62712	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
Novex-2	20896	62911;62912;62913	chr2:178553700;178553699;178553698	chr2:179418427;179418426;179418425
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-105
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.096
• 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/F	rs1343373479	-1.109	0.999	D	0.664	0.693	0.710723107831	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.96E-05	0	None	0	None	0	0	0
Y/F	rs1343373479	-1.109	0.999	D	0.664	0.693	0.710723107831	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	4.7669E-05	0	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
Y/A	0.9943	likely_pathogenic	0.9943	pathogenic	-3.179	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/C	0.9087	likely_pathogenic	0.8953	pathogenic	-1.777	Destabilizing	1.0	D	0.911	deleterious	D	0.63979712	None	None	N
Y/D	0.9931	likely_pathogenic	0.9935	pathogenic	-3.465	Highly Destabilizing	1.0	D	0.929	deleterious	D	0.640200729	None	None	N
Y/E	0.9981	likely_pathogenic	0.9983	pathogenic	-3.237	Highly Destabilizing	1.0	D	0.93	deleterious	None	None	None	None	N
Y/F	0.2756	likely_benign	0.2794	benign	-1.182	Destabilizing	0.999	D	0.664	neutral	D	0.539473425	None	None	N
Y/G	0.9855	likely_pathogenic	0.9853	pathogenic	-3.615	Highly Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
Y/H	0.9732	likely_pathogenic	0.9697	pathogenic	-2.288	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.614259009	None	None	N
Y/I	0.9707	likely_pathogenic	0.9727	pathogenic	-1.72	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9979	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.928	deleterious	None	None	None	None	N
Y/L	0.9514	likely_pathogenic	0.9482	pathogenic	-1.72	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
Y/M	0.9782	likely_pathogenic	0.9786	pathogenic	-1.447	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/N	0.9593	likely_pathogenic	0.9624	pathogenic	-3.119	Highly Destabilizing	1.0	D	0.921	deleterious	D	0.640200729	None	None	N
Y/P	0.9989	likely_pathogenic	0.9989	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
Y/Q	0.9977	likely_pathogenic	0.9976	pathogenic	-2.814	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/R	0.9931	likely_pathogenic	0.9929	pathogenic	-2.137	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
Y/S	0.9796	likely_pathogenic	0.9793	pathogenic	-3.473	Highly Destabilizing	1.0	D	0.928	deleterious	D	0.640200729	None	None	N
Y/T	0.9928	likely_pathogenic	0.9925	pathogenic	-3.118	Highly Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
Y/V	0.9527	likely_pathogenic	0.9533	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/W	0.8654	likely_pathogenic	0.8605	pathogenic	-0.425	Destabilizing	1.0	D	0.791	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.