TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9513	28762;28763;28764	chr2:178709782;178709781;178709780	chr2:179574509;179574508;179574507
N2AB	9196	27811;27812;27813	chr2:178709782;178709781;178709780	chr2:179574509;179574508;179574507
N2A	8269	25030;25031;25032	chr2:178709782;178709781;178709780	chr2:179574509;179574508;179574507
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-81
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.1082
• 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
L/F	rs143420988	-1.227	0.151	None	0.372	0.23	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/F	rs143420988	-1.227	0.151	None	0.372	0.23	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
L/F	rs143420988	-1.227	0.151	None	0.372	0.23	None	gnomAD-4.0.0	6.56616E-06	None	None	None	None	N	None	2.40651E-05	0	None	0	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
L/A	0.8767	likely_pathogenic	0.9041	pathogenic	-2.299	Highly Destabilizing	0.97	D	0.715	prob.delet.	None	None	None	None	N
L/C	0.9308	likely_pathogenic	0.9481	pathogenic	-1.506	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.9994	pathogenic	-2.828	Highly Destabilizing	0.999	D	0.898	deleterious	None	None	None	None	N
L/E	0.9896	likely_pathogenic	0.9943	pathogenic	-2.529	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
L/F	0.4623	ambiguous	0.4925	ambiguous	-1.353	Destabilizing	0.151	N	0.372	neutral	None	None	None	None	N
L/G	0.9835	likely_pathogenic	0.99	pathogenic	-2.873	Highly Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	N
L/H	0.9803	likely_pathogenic	0.9898	pathogenic	-2.417	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/I	0.1492	likely_benign	0.1623	benign	-0.599	Destabilizing	0.248	N	0.301	neutral	None	None	None	None	N
L/K	0.9852	likely_pathogenic	0.9929	pathogenic	-1.835	Destabilizing	0.996	D	0.843	deleterious	None	None	None	None	N
L/M	0.1973	likely_benign	0.2249	benign	-0.617	Destabilizing	0.871	D	0.401	neutral	None	None	None	None	N
L/N	0.9933	likely_pathogenic	0.9967	pathogenic	-2.462	Highly Destabilizing	0.999	D	0.899	deleterious	None	None	None	None	N
L/P	0.9959	likely_pathogenic	0.9976	pathogenic	-1.153	Destabilizing	0.998	D	0.898	deleterious	None	None	None	None	N
L/Q	0.9636	likely_pathogenic	0.9817	pathogenic	-2.151	Highly Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
L/R	0.9741	likely_pathogenic	0.9856	pathogenic	-1.877	Destabilizing	0.994	D	0.874	deleterious	None	None	None	None	N
L/S	0.9857	likely_pathogenic	0.9919	pathogenic	-3.068	Highly Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	N
L/T	0.9207	likely_pathogenic	0.9452	pathogenic	-2.601	Highly Destabilizing	0.985	D	0.782	deleterious	None	None	None	None	N
L/V	0.2285	likely_benign	0.2376	benign	-1.153	Destabilizing	0.835	D	0.574	neutral	None	None	None	None	N
L/W	0.8852	likely_pathogenic	0.9189	pathogenic	-1.712	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/Y	0.9172	likely_pathogenic	0.9384	pathogenic	-1.405	Destabilizing	0.983	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.