TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27834	83725;83726;83727	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
N2AB	26193	78802;78803;78804	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
N2A	25266	76021;76022;76023	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
N2B	18769	56530;56531;56532	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
Novex-1	18894	56905;56906;56907	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
Novex-2	18961	57106;57107;57108	chr2:178562632;178562631;178562630	chr2:179427359;179427358;179427357
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-90
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1867
• 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
C/Y	None	None	0.988	N	0.442	0.324	0.645752913984	gnomAD-4.0.0	6.87609E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.18824E-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
C/A	0.2606	likely_benign	0.2644	benign	-1.835	Destabilizing	0.113	N	0.228	neutral	None	None	None	None	N
C/D	0.625	likely_pathogenic	0.6687	pathogenic	-0.264	Destabilizing	0.115	N	0.341	neutral	None	None	None	None	N
C/E	0.7519	likely_pathogenic	0.7899	pathogenic	-0.159	Destabilizing	0.011	N	0.206	neutral	None	None	None	None	N
C/F	0.1871	likely_benign	0.2034	benign	-1.167	Destabilizing	0.964	D	0.457	neutral	N	0.479900706	None	None	N
C/G	0.1273	likely_benign	0.1266	benign	-2.144	Highly Destabilizing	None	N	0.15	neutral	N	0.422203049	None	None	N
C/H	0.4022	ambiguous	0.451	ambiguous	-2.025	Highly Destabilizing	0.931	D	0.465	neutral	None	None	None	None	N
C/I	0.3951	ambiguous	0.4088	ambiguous	-1.036	Destabilizing	0.911	D	0.453	neutral	None	None	None	None	N
C/K	0.7086	likely_pathogenic	0.7672	pathogenic	-0.961	Destabilizing	0.511	D	0.357	neutral	None	None	None	None	N
C/L	0.3656	ambiguous	0.3823	ambiguous	-1.036	Destabilizing	0.676	D	0.333	neutral	None	None	None	None	N
C/M	0.4815	ambiguous	0.4895	ambiguous	-0.111	Destabilizing	0.991	D	0.419	neutral	None	None	None	None	N
C/N	0.2689	likely_benign	0.2854	benign	-0.951	Destabilizing	0.002	N	0.206	neutral	None	None	None	None	N
C/P	0.9657	likely_pathogenic	0.9695	pathogenic	-1.277	Destabilizing	0.56	D	0.471	neutral	None	None	None	None	N
C/Q	0.4861	ambiguous	0.5417	ambiguous	-0.853	Destabilizing	0.654	D	0.476	neutral	None	None	None	None	N
C/R	0.4366	ambiguous	0.5176	ambiguous	-0.793	Destabilizing	0.792	D	0.487	neutral	N	0.444191687	None	None	N
C/S	0.1548	likely_benign	0.1632	benign	-1.546	Destabilizing	0.006	N	0.155	neutral	N	0.439689944	None	None	N
C/T	0.3013	likely_benign	0.3146	benign	-1.253	Destabilizing	0.218	N	0.335	neutral	None	None	None	None	N
C/V	0.3352	likely_benign	0.3326	benign	-1.277	Destabilizing	0.654	D	0.346	neutral	None	None	None	None	N
C/W	0.54	ambiguous	0.5833	pathogenic	-1.121	Destabilizing	0.997	D	0.414	neutral	N	0.468797891	None	None	N
C/Y	0.2496	likely_benign	0.2947	benign	-1.131	Destabilizing	0.988	D	0.442	neutral	N	0.468544401	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.