TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27935	84028;84029;84030	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
N2AB	26294	79105;79106;79107	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
N2A	25367	76324;76325;76326	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
N2B	18870	56833;56834;56835	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
Novex-1	18995	57208;57209;57210	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
Novex-2	19062	57409;57410;57411	chr2:178562329;178562328;178562327	chr2:179427056;179427055;179427054
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-91
• Domain position: 73
• Structural Position: 107
• Q(SASA): 0.151
• 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
R/K	None	None	0.946	N	0.617	0.422	0.392702134506	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
R/A	0.8663	likely_pathogenic	0.8966	pathogenic	-1.542	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
R/C	0.3442	ambiguous	0.4123	ambiguous	-1.532	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/D	0.9911	likely_pathogenic	0.9931	pathogenic	-0.843	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
R/E	0.876	likely_pathogenic	0.8964	pathogenic	-0.631	Destabilizing	0.993	D	0.578	neutral	None	None	None	None	N
R/F	0.9369	likely_pathogenic	0.9613	pathogenic	-0.679	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
R/G	0.8576	likely_pathogenic	0.8846	pathogenic	-1.886	Destabilizing	0.999	D	0.565	neutral	D	0.558263344	None	None	N
R/H	0.2798	likely_benign	0.3351	benign	-1.775	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	N
R/I	0.8272	likely_pathogenic	0.8692	pathogenic	-0.551	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
R/K	0.37	ambiguous	0.4137	ambiguous	-1.081	Destabilizing	0.946	D	0.617	neutral	N	0.506922639	None	None	N
R/L	0.7358	likely_pathogenic	0.8051	pathogenic	-0.551	Destabilizing	0.999	D	0.565	neutral	None	None	None	None	N
R/M	0.7905	likely_pathogenic	0.8515	pathogenic	-1.128	Destabilizing	1.0	D	0.629	neutral	D	0.526422927	None	None	N
R/N	0.9552	likely_pathogenic	0.9687	pathogenic	-1.128	Destabilizing	1.0	D	0.536	neutral	None	None	None	None	N
R/P	0.9982	likely_pathogenic	0.9984	pathogenic	-0.869	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
R/Q	0.1987	likely_benign	0.2302	benign	-0.911	Destabilizing	0.984	D	0.453	neutral	None	None	None	None	N
R/S	0.8898	likely_pathogenic	0.9187	pathogenic	-1.873	Destabilizing	0.999	D	0.549	neutral	N	0.51875947	None	None	N
R/T	0.8195	likely_pathogenic	0.8768	pathogenic	-1.46	Destabilizing	1.0	D	0.559	neutral	N	0.498124001	None	None	N
R/V	0.8367	likely_pathogenic	0.8793	pathogenic	-0.869	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
R/W	0.6127	likely_pathogenic	0.6894	pathogenic	-0.324	Destabilizing	1.0	D	0.682	prob.neutral	D	0.558516834	None	None	N
R/Y	0.8552	likely_pathogenic	0.8992	pathogenic	-0.139	Destabilizing	1.0	D	0.683	prob.neutral	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.