TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33033	99322;99323;99324	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
N2AB	31392	94399;94400;94401	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
N2A	30465	91618;91619;91620	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
N2B	23968	72127;72128;72129	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
Novex-1	24093	72502;72503;72504	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
Novex-2	24160	72703;72704;72705	chr2:178538732;178538731;178538730	chr2:179403459;179403458;179403457
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: Fn3-129
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1019
• 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/H	None	None	1.0	D	0.811	0.874	0.729785666219	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.9928	likely_pathogenic	0.9945	pathogenic	-3.361	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/C	0.8012	likely_pathogenic	0.8513	pathogenic	-1.885	Destabilizing	1.0	D	0.873	deleterious	D	0.654673505	None	None	N
Y/D	0.9947	likely_pathogenic	0.9949	pathogenic	-3.853	Highly Destabilizing	1.0	D	0.918	deleterious	D	0.671126835	None	None	N
Y/E	0.9981	likely_pathogenic	0.9984	pathogenic	-3.634	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/F	0.172	likely_benign	0.2111	benign	-1.354	Destabilizing	0.999	D	0.647	neutral	D	0.581129108	None	None	N
Y/G	0.983	likely_pathogenic	0.9843	pathogenic	-3.775	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
Y/H	0.9533	likely_pathogenic	0.9679	pathogenic	-2.474	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.654269897	None	None	N
Y/I	0.95	likely_pathogenic	0.959	pathogenic	-1.963	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9984	pathogenic	-2.585	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/L	0.9147	likely_pathogenic	0.9303	pathogenic	-1.963	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
Y/M	0.9723	likely_pathogenic	0.9793	pathogenic	-1.632	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
Y/N	0.9531	likely_pathogenic	0.959	pathogenic	-3.44	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.670925031	None	None	N
Y/P	0.9992	likely_pathogenic	0.9992	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
Y/Q	0.9964	likely_pathogenic	0.9972	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
Y/R	0.9932	likely_pathogenic	0.9943	pathogenic	-2.378	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
Y/S	0.9666	likely_pathogenic	0.9732	pathogenic	-3.715	Highly Destabilizing	1.0	D	0.899	deleterious	D	0.670925031	None	None	N
Y/T	0.9888	likely_pathogenic	0.9912	pathogenic	-3.377	Highly Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/V	0.9258	likely_pathogenic	0.9404	pathogenic	-2.448	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
Y/W	0.765	likely_pathogenic	0.8132	pathogenic	-0.633	Destabilizing	1.0	D	0.803	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.