TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20798	62617;62618;62619	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
N2AB	19157	57694;57695;57696	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
N2A	18230	54913;54914;54915	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
N2B	11733	35422;35423;35424	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
Novex-1	11858	35797;35798;35799	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
Novex-2	11925	35998;35999;36000	chr2:178589333;178589332;178589331	chr2:179454060;179454059;179454058
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-122
• Domain position: 30
• Structural Position: 43
• Q(SASA): 0.4547
• 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
F/L	None	None	0.425	N	0.226	0.236	0.101711395817	gnomAD-4.0.0	1.08029E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18125E-05	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
F/A	0.2338	likely_benign	0.2096	benign	-1.431	Destabilizing	0.495	N	0.426	neutral	None	None	None	None	I
F/C	0.234	likely_benign	0.2588	benign	-0.39	Destabilizing	0.993	D	0.495	neutral	N	0.478878343	None	None	I
F/D	0.5764	likely_pathogenic	0.5428	ambiguous	0.149	Stabilizing	0.495	N	0.515	neutral	None	None	None	None	I
F/E	0.538	ambiguous	0.5266	ambiguous	0.154	Stabilizing	0.176	N	0.433	neutral	None	None	None	None	I
F/G	0.6065	likely_pathogenic	0.5521	ambiguous	-1.678	Destabilizing	0.495	N	0.521	neutral	None	None	None	None	I
F/H	0.3646	ambiguous	0.3334	benign	-0.2	Destabilizing	0.944	D	0.475	neutral	None	None	None	None	I
F/I	0.125	likely_benign	0.1095	benign	-0.755	Destabilizing	0.784	D	0.287	neutral	N	0.410653195	None	None	I
F/K	0.5364	ambiguous	0.4907	ambiguous	-0.442	Destabilizing	0.013	N	0.214	neutral	None	None	None	None	I
F/L	0.5287	ambiguous	0.4838	ambiguous	-0.755	Destabilizing	0.425	N	0.226	neutral	N	0.394606307	None	None	I
F/M	0.2675	likely_benign	0.2616	benign	-0.51	Destabilizing	0.944	D	0.363	neutral	None	None	None	None	I
F/N	0.3241	likely_benign	0.2887	benign	-0.354	Destabilizing	0.704	D	0.536	neutral	None	None	None	None	I
F/P	0.5954	likely_pathogenic	0.5834	pathogenic	-0.965	Destabilizing	0.828	D	0.547	neutral	None	None	None	None	I
F/Q	0.3828	ambiguous	0.3567	ambiguous	-0.453	Destabilizing	0.004	N	0.22	neutral	None	None	None	None	I
F/R	0.476	ambiguous	0.4332	ambiguous	0.117	Stabilizing	0.329	N	0.519	neutral	None	None	None	None	I
F/S	0.1986	likely_benign	0.1665	benign	-1.044	Destabilizing	0.425	N	0.449	neutral	N	0.409439687	None	None	I
F/T	0.2489	likely_benign	0.222	benign	-0.949	Destabilizing	0.495	N	0.489	neutral	None	None	None	None	I
F/V	0.1154	likely_benign	0.1002	benign	-0.965	Destabilizing	0.6	D	0.44	neutral	N	0.376020547	None	None	I
F/W	0.487	ambiguous	0.4744	ambiguous	-0.421	Destabilizing	0.981	D	0.41	neutral	None	None	None	None	I
F/Y	0.1197	likely_benign	0.1217	benign	-0.46	Destabilizing	0.917	D	0.329	neutral	N	0.460119224	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.