TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34037	102334;102335;102336	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
N2AB	32396	97411;97412;97413	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
N2A	31469	94630;94631;94632	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
N2B	24972	75139;75140;75141	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
Novex-1	25097	75514;75515;75516	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
Novex-2	25164	75715;75716;75717	chr2:178534506;178534505;178534504	chr2:179399233;179399232;179399231
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Kinase-1
• Domain position: 225
• Q(SASA): 0.6493
• Predicted PPI site: I

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
E/A	None	None	None	N	None	0.466	0.487419150623	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
E/A	0.2196	likely_benign	0.1982	benign	-0.164	Destabilizing	None	None	None	None	N	0.475163247	None	None	I
E/C	0.9444	likely_pathogenic	0.9406	pathogenic	-0.06	Destabilizing	None	None	None	None	None	None	None	None	I
E/D	0.1649	likely_benign	0.165	benign	-0.16	Destabilizing	None	None	None	None	N	0.455577408	None	None	I
E/F	0.8896	likely_pathogenic	0.8606	pathogenic	-0.17	Destabilizing	None	None	None	None	None	None	None	None	I
E/G	0.3118	likely_benign	0.2956	benign	-0.316	Destabilizing	None	None	None	None	N	0.496578669	None	None	I
E/H	0.6787	likely_pathogenic	0.6552	pathogenic	0.259	Stabilizing	None	None	None	None	None	None	None	None	I
E/I	0.5799	likely_pathogenic	0.5459	ambiguous	0.188	Stabilizing	None	None	None	None	None	None	None	None	I
E/K	0.2875	likely_benign	0.2432	benign	0.359	Stabilizing	None	None	None	None	N	0.431719114	None	None	I
E/L	0.6373	likely_pathogenic	0.5833	pathogenic	0.188	Stabilizing	None	None	None	None	None	None	None	None	I
E/M	0.6777	likely_pathogenic	0.6482	pathogenic	0.107	Stabilizing	None	None	None	None	None	None	None	None	I
E/N	0.3824	ambiguous	0.3748	ambiguous	0.19	Stabilizing	None	None	None	None	None	None	None	None	I
E/P	0.6807	likely_pathogenic	0.6688	pathogenic	0.09	Stabilizing	None	None	None	None	None	None	None	None	I
E/Q	0.299	likely_benign	0.2869	benign	0.208	Stabilizing	None	None	None	None	N	0.479742347	None	None	I
E/R	0.4535	ambiguous	0.4003	ambiguous	0.584	Stabilizing	None	None	None	None	None	None	None	None	I
E/S	0.332	likely_benign	0.3186	benign	0.001	Stabilizing	None	None	None	None	None	None	None	None	I
E/T	0.3377	likely_benign	0.3192	benign	0.124	Stabilizing	None	None	None	None	None	None	None	None	I
E/V	0.3749	ambiguous	0.3505	ambiguous	0.09	Stabilizing	None	None	None	None	N	0.484110804	None	None	I
E/W	0.9637	likely_pathogenic	0.9553	pathogenic	-0.094	Destabilizing	None	None	None	None	None	None	None	None	I
E/Y	0.7852	likely_pathogenic	0.7491	pathogenic	0.057	Stabilizing	None	None	None	None	None	None	None	None	I

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.