TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25077	75454;75455;75456	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
N2AB	23436	70531;70532;70533	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
N2A	22509	67750;67751;67752	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
N2B	16012	48259;48260;48261	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
Novex-1	16137	48634;48635;48636	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
Novex-2	16204	48835;48836;48837	chr2:178570903;178570902;178570901	chr2:179435630;179435629;179435628
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: Fn3-70
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0893
• 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	rs1001172074	None	1.0	D	0.87	0.862	0.922390740026	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs1001172074	None	1.0	D	0.87	0.862	0.922390740026	gnomAD-4.0.0	1.05365E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44114E-05	0	0
Y/H	None	None	1.0	D	0.849	0.831	0.830002795327	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	2.77485E-05	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
Y/A	0.9886	likely_pathogenic	0.988	pathogenic	-3.498	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/C	0.7746	likely_pathogenic	0.7809	pathogenic	-1.89	Destabilizing	1.0	D	0.87	deleterious	D	0.65575571	None	None	N
Y/D	0.9907	likely_pathogenic	0.9873	pathogenic	-3.975	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.688026597	None	None	N
Y/E	0.9968	likely_pathogenic	0.996	pathogenic	-3.762	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/F	0.2564	likely_benign	0.2524	benign	-1.559	Destabilizing	0.999	D	0.742	deleterious	D	0.620275597	None	None	N
Y/G	0.9734	likely_pathogenic	0.9677	pathogenic	-3.892	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/H	0.9435	likely_pathogenic	0.9276	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.671775071	None	None	N
Y/I	0.954	likely_pathogenic	0.9556	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9971	likely_pathogenic	0.9964	pathogenic	-2.697	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/L	0.9312	likely_pathogenic	0.9307	pathogenic	-2.155	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
Y/M	0.9641	likely_pathogenic	0.9648	pathogenic	-1.77	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9483	likely_pathogenic	0.9324	pathogenic	-3.539	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.687824793	None	None	N
Y/P	0.9985	likely_pathogenic	0.998	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/Q	0.9936	likely_pathogenic	0.9926	pathogenic	-3.26	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/R	0.9904	likely_pathogenic	0.9893	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/S	0.9643	likely_pathogenic	0.9561	pathogenic	-3.777	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.688026597	None	None	N
Y/T	0.9865	likely_pathogenic	0.9848	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/V	0.9054	likely_pathogenic	0.9081	pathogenic	-2.622	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/W	0.7671	likely_pathogenic	0.7525	pathogenic	-0.865	Destabilizing	1.0	D	0.826	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.