TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26123	78592;78593;78594	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
N2AB	24482	73669;73670;73671	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
N2A	23555	70888;70889;70890	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
N2B	17058	51397;51398;51399	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
Novex-1	17183	51772;51773;51774	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
Novex-2	17250	51973;51974;51975	chr2:178567765;178567764;178567763	chr2:179432492;179432491;179432490
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: Fn3-78
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0958
• 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	0.847	0.868	0.842149753793	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Y/N	rs1706474131	None	1.0	D	0.855	0.844	0.88723069334	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9987	likely_pathogenic	0.9985	pathogenic	-3.594	Highly Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
Y/C	0.9578	likely_pathogenic	0.9411	pathogenic	-2.078	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.662501049	None	None	N
Y/D	0.9985	likely_pathogenic	0.9984	pathogenic	-3.919	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.662702853	None	None	N
Y/E	0.9996	likely_pathogenic	0.9995	pathogenic	-3.708	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/F	0.368	ambiguous	0.3335	benign	-1.371	Destabilizing	0.999	D	0.661	neutral	N	0.519154086	None	None	N
Y/G	0.9951	likely_pathogenic	0.9947	pathogenic	-3.994	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/H	0.9914	likely_pathogenic	0.9902	pathogenic	-2.616	Highly Destabilizing	1.0	D	0.796	deleterious	D	0.646279883	None	None	N
Y/I	0.9899	likely_pathogenic	0.9868	pathogenic	-2.231	Highly Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
Y/K	0.9995	likely_pathogenic	0.9995	pathogenic	-2.536	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/L	0.973	likely_pathogenic	0.9695	pathogenic	-2.231	Highly Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
Y/M	0.9924	likely_pathogenic	0.9904	pathogenic	-1.975	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/N	0.986	likely_pathogenic	0.9855	pathogenic	-3.313	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.662702853	None	None	N
Y/P	0.9997	likely_pathogenic	0.9997	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
Y/Q	0.9994	likely_pathogenic	0.9993	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
Y/R	0.9979	likely_pathogenic	0.9977	pathogenic	-2.257	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
Y/S	0.9941	likely_pathogenic	0.9933	pathogenic	-3.626	Highly Destabilizing	1.0	D	0.847	deleterious	D	0.662702853	None	None	N
Y/T	0.9983	likely_pathogenic	0.9979	pathogenic	-3.3	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/V	0.9815	likely_pathogenic	0.9763	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
Y/W	0.9216	likely_pathogenic	0.9032	pathogenic	-0.599	Destabilizing	1.0	D	0.787	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.