TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18655	56188;56189;56190	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
N2AB	17014	51265;51266;51267	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
N2A	16087	48484;48485;48486	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
N2B	9590	28993;28994;28995	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
Novex-1	9715	29368;29369;29370	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
Novex-2	9782	29569;29570;29571	chr2:178600941;178600940;178600939	chr2:179465668;179465667;179465666
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: Fn3-23
• Domain position: 77
• Structural Position: 104
• Q(SASA): 0.0682
• 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	rs1391393842	None	1.0	D	0.848	0.842	0.803198302387	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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	0.9769	likely_pathogenic	0.9722	pathogenic	-2.807	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
Y/C	0.8249	likely_pathogenic	0.774	pathogenic	-1.671	Destabilizing	1.0	D	0.848	deleterious	D	0.640432843	None	None	N
Y/D	0.9858	likely_pathogenic	0.9819	pathogenic	-2.916	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.67270373	None	None	N
Y/E	0.9931	likely_pathogenic	0.9913	pathogenic	-2.718	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
Y/F	0.2224	likely_benign	0.2249	benign	-0.928	Destabilizing	0.999	D	0.728	prob.delet.	D	0.607970871	None	None	N
Y/G	0.9668	likely_pathogenic	0.9608	pathogenic	-3.23	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/H	0.9025	likely_pathogenic	0.8713	pathogenic	-1.773	Destabilizing	1.0	D	0.787	deleterious	D	0.647165618	None	None	N
Y/I	0.9218	likely_pathogenic	0.9166	pathogenic	-1.423	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
Y/K	0.9875	likely_pathogenic	0.9845	pathogenic	-1.987	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
Y/L	0.8965	likely_pathogenic	0.8911	pathogenic	-1.423	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
Y/M	0.9252	likely_pathogenic	0.9183	pathogenic	-1.183	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
Y/N	0.8947	likely_pathogenic	0.8728	pathogenic	-2.731	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.672501926	None	None	N
Y/P	0.9991	likely_pathogenic	0.9989	pathogenic	-1.896	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/Q	0.9857	likely_pathogenic	0.9814	pathogenic	-2.484	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/R	0.9731	likely_pathogenic	0.9658	pathogenic	-1.772	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/S	0.9558	likely_pathogenic	0.9449	pathogenic	-3.144	Highly Destabilizing	1.0	D	0.818	deleterious	D	0.67270373	None	None	N
Y/T	0.9736	likely_pathogenic	0.9653	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/V	0.8615	likely_pathogenic	0.8544	pathogenic	-1.896	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
Y/W	0.7261	likely_pathogenic	0.7243	pathogenic	-0.285	Destabilizing	1.0	D	0.764	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.