TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9540	28843;28844;28845	chr2:178709701;178709700;178709699	chr2:179574428;179574427;179574426
N2AB	9223	27892;27893;27894	chr2:178709701;178709700;178709699	chr2:179574428;179574427;179574426
N2A	8296	25111;25112;25113	chr2:178709701;178709700;178709699	chr2:179574428;179574427;179574426
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-81
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.2623
• 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/W	None	None	0.927	None	0.597	0.418	0.730682531328	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
C/Y	rs1427971848	None	0.001	None	0.415	0.23	0.475034548194	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
C/A	0.359	ambiguous	0.3189	benign	-1.647	Destabilizing	0.495	N	0.382	neutral	None	None	None	None	N
C/D	0.7461	likely_pathogenic	0.6783	pathogenic	-0.885	Destabilizing	0.543	D	0.607	neutral	None	None	None	None	N
C/E	0.7851	likely_pathogenic	0.7398	pathogenic	-0.757	Destabilizing	0.704	D	0.603	neutral	None	None	None	None	N
C/F	0.1799	likely_benign	0.183	benign	-1.094	Destabilizing	0.473	N	0.547	neutral	None	None	None	None	N
C/G	0.2366	likely_benign	0.1943	benign	-1.97	Destabilizing	0.473	N	0.57	neutral	None	None	None	None	N
C/H	0.4259	ambiguous	0.4083	ambiguous	-2.208	Highly Destabilizing	0.893	D	0.645	neutral	None	None	None	None	N
C/I	0.3321	likely_benign	0.3284	benign	-0.815	Destabilizing	0.704	D	0.557	neutral	None	None	None	None	N
C/K	0.774	likely_pathogenic	0.7348	pathogenic	-1.119	Destabilizing	0.704	D	0.606	neutral	None	None	None	None	N
C/L	0.3714	ambiguous	0.3472	ambiguous	-0.815	Destabilizing	0.329	N	0.475	neutral	None	None	None	None	N
C/M	0.4947	ambiguous	0.5012	ambiguous	0.038	Stabilizing	0.981	D	0.613	neutral	None	None	None	None	N
C/N	0.4454	ambiguous	0.4382	ambiguous	-1.224	Destabilizing	0.007	N	0.481	neutral	None	None	None	None	N
C/P	0.9818	likely_pathogenic	0.9701	pathogenic	-1.066	Destabilizing	0.981	D	0.633	neutral	None	None	None	None	N
C/Q	0.5894	likely_pathogenic	0.5482	ambiguous	-1.083	Destabilizing	0.944	D	0.632	neutral	None	None	None	None	N
C/R	0.4247	ambiguous	0.3642	ambiguous	-1.136	Destabilizing	0.863	D	0.635	neutral	None	None	None	None	N
C/S	0.2367	likely_benign	0.2113	benign	-1.67	Destabilizing	0.27	N	0.512	neutral	None	None	None	None	N
C/T	0.2612	likely_benign	0.2402	benign	-1.36	Destabilizing	0.704	D	0.528	neutral	None	None	None	None	N
C/V	0.2969	likely_benign	0.2851	benign	-1.066	Destabilizing	0.704	D	0.533	neutral	None	None	None	None	N
C/W	0.405	ambiguous	0.3663	ambiguous	-1.217	Destabilizing	0.927	D	0.597	neutral	None	None	None	None	N
C/Y	0.1767	likely_benign	0.1792	benign	-1.124	Destabilizing	0.001	N	0.415	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.