TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14922	44989;44990;44991	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
N2AB	13281	40066;40067;40068	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
N2A	12354	37285;37286;37287	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
N2B	5857	17794;17795;17796	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
Novex-1	5982	18169;18170;18171	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
Novex-2	6049	18370;18371;18372	chr2:178624516;178624515;178624514	chr2:179489243;179489242;179489241
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: Ig-100
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.1335
• 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/D	rs1576599425	None	1.0	D	0.887	0.65	0.372268306217	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94477E-04	None	0	0	0	0	0
Y/H	None	None	1.0	D	0.807	0.576	0.362960570912	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.9949	likely_pathogenic	0.9953	pathogenic	-2.728	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/C	0.9562	likely_pathogenic	0.9547	pathogenic	-2.094	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.680844841	None	None	N
Y/D	0.9964	likely_pathogenic	0.998	pathogenic	-3.563	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.680844841	None	None	N
Y/E	0.9987	likely_pathogenic	0.9992	pathogenic	-3.321	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/F	0.2693	likely_benign	0.3135	benign	-1.12	Destabilizing	0.999	D	0.687	prob.neutral	N	0.496771749	None	None	N
Y/G	0.9913	likely_pathogenic	0.9926	pathogenic	-3.181	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/H	0.9799	likely_pathogenic	0.9849	pathogenic	-2.429	Highly Destabilizing	1.0	D	0.807	deleterious	D	0.680844841	None	None	N
Y/I	0.94	likely_pathogenic	0.9499	pathogenic	-1.217	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/K	0.9987	likely_pathogenic	0.9992	pathogenic	-2.458	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/L	0.9031	likely_pathogenic	0.903	pathogenic	-1.217	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
Y/M	0.9817	likely_pathogenic	0.9834	pathogenic	-1.233	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/N	0.9848	likely_pathogenic	0.9875	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.680844841	None	None	N
Y/P	0.998	likely_pathogenic	0.9982	pathogenic	-1.739	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.9986	likely_pathogenic	0.999	pathogenic	-3.011	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/R	0.9946	likely_pathogenic	0.9961	pathogenic	-2.598	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/S	0.9868	likely_pathogenic	0.9878	pathogenic	-3.713	Highly Destabilizing	1.0	D	0.901	deleterious	D	0.680844841	None	None	N
Y/T	0.9948	likely_pathogenic	0.9954	pathogenic	-3.324	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/V	0.9046	likely_pathogenic	0.9057	pathogenic	-1.739	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/W	0.8179	likely_pathogenic	0.8105	pathogenic	-0.523	Destabilizing	1.0	D	0.793	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.