TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7801	23626;23627;23628	chr2:178720241;178720240;178720239	chr2:179584968;179584967;179584966
N2AB	7484	22675;22676;22677	chr2:178720241;178720240;178720239	chr2:179584968;179584967;179584966
N2A	6557	19894;19895;19896	chr2:178720241;178720240;178720239	chr2:179584968;179584967;179584966
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-63
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2593
• 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
L/V	None	None	0.624	N	0.473	0.124	0.324161360171	gnomAD-4.0.0	6.85611E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16621E-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
L/A	0.7492	likely_pathogenic	0.7501	pathogenic	-2.104	Highly Destabilizing	0.996	D	0.515	neutral	None	None	None	None	N
L/C	0.8944	likely_pathogenic	0.8864	pathogenic	-1.479	Destabilizing	0.82	D	0.393	neutral	None	None	None	None	N
L/D	0.9896	likely_pathogenic	0.9922	pathogenic	-1.352	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/E	0.9602	likely_pathogenic	0.9688	pathogenic	-1.216	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/F	0.5239	ambiguous	0.5505	ambiguous	-1.3	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
L/G	0.9462	likely_pathogenic	0.9527	pathogenic	-2.575	Highly Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
L/H	0.9372	likely_pathogenic	0.9557	pathogenic	-1.844	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
L/I	0.1039	likely_benign	0.1049	benign	-0.804	Destabilizing	0.076	N	0.253	neutral	N	0.513643411	None	None	N
L/K	0.9626	likely_pathogenic	0.9733	pathogenic	-1.285	Destabilizing	0.994	D	0.758	deleterious	None	None	None	None	N
L/M	0.2504	likely_benign	0.2362	benign	-0.771	Destabilizing	0.996	D	0.649	neutral	None	None	None	None	N
L/N	0.9428	likely_pathogenic	0.9561	pathogenic	-1.303	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/P	0.3965	ambiguous	0.366	ambiguous	-1.211	Destabilizing	1.0	D	0.807	deleterious	N	0.441585738	None	None	N
L/Q	0.8889	likely_pathogenic	0.9128	pathogenic	-1.288	Destabilizing	0.999	D	0.769	deleterious	N	0.5192025	None	None	N
L/R	0.9323	likely_pathogenic	0.9507	pathogenic	-0.964	Destabilizing	0.999	D	0.774	deleterious	N	0.5192025	None	None	N
L/S	0.9318	likely_pathogenic	0.9448	pathogenic	-2.131	Highly Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
L/T	0.8051	likely_pathogenic	0.8149	pathogenic	-1.848	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
L/V	0.1727	likely_benign	0.1564	benign	-1.211	Destabilizing	0.624	D	0.473	neutral	N	0.47078831	None	None	N
L/W	0.8944	likely_pathogenic	0.9168	pathogenic	-1.46	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
L/Y	0.9261	likely_pathogenic	0.9405	pathogenic	-1.198	Destabilizing	0.996	D	0.755	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.