TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17504	52735;52736;52737	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
N2AB	15863	47812;47813;47814	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
N2A	14936	45031;45032;45033	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
N2B	8439	25540;25541;25542	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
Novex-1	8564	25915;25916;25917	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
Novex-2	8631	26116;26117;26118	chr2:178608373;178608372;178608371	chr2:179473100;179473099;179473098
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: Fn3-15
• Domain position: 35
• Structural Position: 38
• Q(SASA): 0.0809
• 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	rs1343011962	-1.812	1.0	D	0.906	0.907	0.851035771418	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.3E-05	None	0	0	0
Y/C	rs1343011962	-1.812	1.0	D	0.906	0.907	0.851035771418	gnomAD-4.0.0	1.59562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4374E-05	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	0.998	likely_pathogenic	0.998	pathogenic	-3.255	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
Y/C	0.932	likely_pathogenic	0.9369	pathogenic	-1.629	Destabilizing	1.0	D	0.906	deleterious	D	0.657227317	None	None	N
Y/D	0.9979	likely_pathogenic	0.9976	pathogenic	-3.69	Highly Destabilizing	1.0	D	0.93	deleterious	D	0.657429121	None	None	N
Y/E	0.9993	likely_pathogenic	0.9993	pathogenic	-3.471	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
Y/F	0.2352	likely_benign	0.2552	benign	-1.388	Destabilizing	0.999	D	0.645	neutral	D	0.571378193	None	None	N
Y/G	0.9927	likely_pathogenic	0.9932	pathogenic	-3.652	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
Y/H	0.9832	likely_pathogenic	0.9828	pathogenic	-2.548	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.656823708	None	None	N
Y/I	0.9767	likely_pathogenic	0.9734	pathogenic	-1.902	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9982	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
Y/L	0.9637	likely_pathogenic	0.961	pathogenic	-1.902	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
Y/M	0.989	likely_pathogenic	0.9893	pathogenic	-1.583	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
Y/N	0.9835	likely_pathogenic	0.9818	pathogenic	-3.173	Highly Destabilizing	1.0	D	0.922	deleterious	D	0.657227317	None	None	N
Y/P	0.9994	likely_pathogenic	0.9993	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.947	deleterious	None	None	None	None	N
Y/Q	0.9987	likely_pathogenic	0.9985	pathogenic	-2.877	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/R	0.9952	likely_pathogenic	0.9943	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
Y/S	0.9913	likely_pathogenic	0.9912	pathogenic	-3.422	Highly Destabilizing	1.0	D	0.923	deleterious	D	0.657227317	None	None	N
Y/T	0.9969	likely_pathogenic	0.9969	pathogenic	-3.084	Highly Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	N
Y/V	0.9634	likely_pathogenic	0.9606	pathogenic	-2.373	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
Y/W	0.8519	likely_pathogenic	0.8557	pathogenic	-0.659	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.