TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20410	61453;61454;61455	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
N2AB	18769	56530;56531;56532	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
N2A	17842	53749;53750;53751	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
N2B	11345	34258;34259;34260	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
Novex-1	11470	34633;34634;34635	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
Novex-2	11537	34834;34835;34836	chr2:178590497;178590496;178590495	chr2:179455224;179455223;179455222
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: Fn3-36
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.0839
• 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	rs2049975151	None	None	N	0.634	0.158	0.412458657427	gnomAD-4.0.0	1.36892E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99726E-07	0	1.657E-05

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	0.4691	ambiguous	0.4135	ambiguous	-1.443	Destabilizing	0.067	N	0.636	neutral	None	None	None	None	N
C/D	0.95	likely_pathogenic	0.8954	pathogenic	-1.661	Destabilizing	0.555	D	0.823	deleterious	None	None	None	None	N
C/E	0.918	likely_pathogenic	0.8499	pathogenic	-1.412	Destabilizing	0.555	D	0.821	deleterious	None	None	None	None	N
C/F	0.1746	likely_benign	0.1303	benign	-0.86	Destabilizing	0.188	N	0.796	deleterious	N	0.461049438	None	None	N
C/G	0.419	ambiguous	0.3542	ambiguous	-1.787	Destabilizing	0.211	N	0.82	deleterious	N	0.478424478	None	None	N
C/H	0.67	likely_pathogenic	0.5282	ambiguous	-2.024	Highly Destabilizing	0.38	N	0.791	deleterious	None	None	None	None	N
C/I	0.3892	ambiguous	0.3078	benign	-0.503	Destabilizing	0.081	N	0.757	deleterious	None	None	None	None	N
C/K	0.8748	likely_pathogenic	0.8049	pathogenic	-1.064	Destabilizing	0.38	N	0.826	deleterious	None	None	None	None	N
C/L	0.3958	ambiguous	0.32	benign	-0.503	Destabilizing	0.035	N	0.653	neutral	None	None	None	None	N
C/M	0.3942	ambiguous	0.3612	ambiguous	-0.022	Destabilizing	0.007	N	0.529	neutral	None	None	None	None	N
C/N	0.7924	likely_pathogenic	0.6837	pathogenic	-1.749	Destabilizing	0.555	D	0.819	deleterious	None	None	None	None	N
C/P	0.9982	likely_pathogenic	0.9956	pathogenic	-0.797	Destabilizing	0.791	D	0.821	deleterious	None	None	None	None	N
C/Q	0.7248	likely_pathogenic	0.6258	pathogenic	-1.217	Destabilizing	0.555	D	0.819	deleterious	None	None	None	None	N
C/R	0.6775	likely_pathogenic	0.5594	ambiguous	-1.569	Destabilizing	0.317	N	0.823	deleterious	N	0.425379427	None	None	N
C/S	0.4386	ambiguous	0.3606	ambiguous	-1.983	Destabilizing	0.117	N	0.762	deleterious	N	0.439924805	None	None	N
C/T	0.5928	likely_pathogenic	0.5154	ambiguous	-1.564	Destabilizing	0.149	N	0.759	deleterious	None	None	None	None	N
C/V	0.3538	ambiguous	0.3029	benign	-0.797	Destabilizing	0.081	N	0.707	prob.neutral	None	None	None	None	N
C/W	0.5174	ambiguous	0.3999	ambiguous	-1.359	Destabilizing	0.78	D	0.745	deleterious	N	0.479115124	None	None	N
C/Y	0.2177	likely_benign	0.1463	benign	-1.107	Destabilizing	None	N	0.634	neutral	N	0.399416616	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.