TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29584	88975;88976;88977	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
N2AB	27943	84052;84053;84054	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
N2A	27016	81271;81272;81273	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
N2B	20519	61780;61781;61782	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
Novex-1	20644	62155;62156;62157	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
Novex-2	20711	62356;62357;62358	chr2:178554597;178554596;178554595	chr2:179419324;179419323;179419322
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-103
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.2907
• Predicted PPI site: I

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
V/A	rs1356142891	-1.364	0.939	N	0.487	0.335	0.51759925163	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
V/A	rs1356142891	-1.364	0.939	N	0.487	0.335	0.51759925163	gnomAD-4.0.0	3.18202E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.71549E-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
V/A	0.4363	ambiguous	0.4303	ambiguous	-1.145	Destabilizing	0.939	D	0.487	neutral	N	0.466849334	None	None	I
V/C	0.8794	likely_pathogenic	0.8803	pathogenic	-0.947	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	I
V/D	0.9428	likely_pathogenic	0.9362	pathogenic	-0.385	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	I
V/E	0.8631	likely_pathogenic	0.8579	pathogenic	-0.354	Destabilizing	0.997	D	0.791	deleterious	N	0.502880033	None	None	I
V/F	0.4715	ambiguous	0.4578	ambiguous	-0.745	Destabilizing	0.986	D	0.813	deleterious	None	None	None	None	I
V/G	0.7346	likely_pathogenic	0.7287	pathogenic	-1.482	Destabilizing	0.997	D	0.795	deleterious	N	0.50917391	None	None	I
V/H	0.9464	likely_pathogenic	0.9467	pathogenic	-0.884	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
V/I	0.0952	likely_benign	0.0922	benign	-0.325	Destabilizing	0.06	N	0.238	neutral	None	None	None	None	I
V/K	0.9334	likely_pathogenic	0.9339	pathogenic	-0.841	Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	I
V/L	0.3508	ambiguous	0.3008	benign	-0.325	Destabilizing	0.76	D	0.425	neutral	N	0.47822969	None	None	I
V/M	0.3412	ambiguous	0.2772	benign	-0.403	Destabilizing	0.982	D	0.718	prob.delet.	N	0.501033609	None	None	I
V/N	0.8741	likely_pathogenic	0.8543	pathogenic	-0.759	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	I
V/P	0.9617	likely_pathogenic	0.9582	pathogenic	-0.562	Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	I
V/Q	0.8633	likely_pathogenic	0.8572	pathogenic	-0.811	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	I
V/R	0.9144	likely_pathogenic	0.9191	pathogenic	-0.475	Destabilizing	0.998	D	0.82	deleterious	None	None	None	None	I
V/S	0.732	likely_pathogenic	0.7179	pathogenic	-1.396	Destabilizing	0.993	D	0.779	deleterious	None	None	None	None	I
V/T	0.5961	likely_pathogenic	0.5725	pathogenic	-1.228	Destabilizing	0.953	D	0.605	neutral	None	None	None	None	I
V/W	0.9748	likely_pathogenic	0.9755	pathogenic	-0.919	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
V/Y	0.8861	likely_pathogenic	0.8865	pathogenic	-0.59	Destabilizing	0.998	D	0.818	deleterious	None	None	None	None	I

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.