TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27347	82264;82265;82266	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
N2AB	25706	77341;77342;77343	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
N2A	24779	74560;74561;74562	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
N2B	18282	55069;55070;55071	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
Novex-1	18407	55444;55445;55446	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
Novex-2	18474	55645;55646;55647	chr2:178564093;178564092;178564091	chr2:179428820;179428819;179428818
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: Ig-140
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.1027
• 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	None	None	1.0	D	0.865	0.771	0.805993168017	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
Y/H	None	None	0.998	D	0.706	0.819	0.676191613372	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85847E-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	0.996	likely_pathogenic	0.9965	pathogenic	-2.196	Highly Destabilizing	0.985	D	0.823	deleterious	None	None	None	None	N
Y/C	0.9129	likely_pathogenic	0.9185	pathogenic	-1.524	Destabilizing	1.0	D	0.865	deleterious	D	0.647387115	None	None	N
Y/D	0.9966	likely_pathogenic	0.9974	pathogenic	-2.79	Highly Destabilizing	0.998	D	0.879	deleterious	D	0.647387115	None	None	N
Y/E	0.9987	likely_pathogenic	0.999	pathogenic	-2.536	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
Y/F	0.1912	likely_benign	0.1757	benign	-0.795	Destabilizing	0.031	N	0.395	neutral	D	0.553694395	None	None	N
Y/G	0.9913	likely_pathogenic	0.9918	pathogenic	-2.653	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
Y/H	0.9564	likely_pathogenic	0.958	pathogenic	-2.157	Highly Destabilizing	0.998	D	0.706	prob.neutral	D	0.63116595	None	None	N
Y/I	0.9352	likely_pathogenic	0.9435	pathogenic	-0.681	Destabilizing	0.97	D	0.803	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9984	pathogenic	-1.796	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
Y/L	0.9005	likely_pathogenic	0.9077	pathogenic	-0.681	Destabilizing	0.871	D	0.759	deleterious	None	None	None	None	N
Y/M	0.9682	likely_pathogenic	0.9718	pathogenic	-0.768	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
Y/N	0.9791	likely_pathogenic	0.982	pathogenic	-2.72	Highly Destabilizing	0.998	D	0.856	deleterious	D	0.647387115	None	None	N
Y/P	0.9992	likely_pathogenic	0.9994	pathogenic	-1.203	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
Y/Q	0.9979	likely_pathogenic	0.9981	pathogenic	-2.233	Highly Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
Y/R	0.9946	likely_pathogenic	0.9949	pathogenic	-2.151	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
Y/S	0.9916	likely_pathogenic	0.9925	pathogenic	-3.022	Highly Destabilizing	0.998	D	0.823	deleterious	D	0.647387115	None	None	N
Y/T	0.9956	likely_pathogenic	0.9963	pathogenic	-2.616	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
Y/V	0.9172	likely_pathogenic	0.9248	pathogenic	-1.203	Destabilizing	0.97	D	0.785	deleterious	None	None	None	None	N
Y/W	0.8075	likely_pathogenic	0.8132	pathogenic	-0.195	Destabilizing	0.999	D	0.719	prob.delet.	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.