TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5370	16333;16334;16335	chr2:178733068;178733067;178733066	chr2:179597795;179597794;179597793
N2AB	5053	15382;15383;15384	chr2:178733068;178733067;178733066	chr2:179597795;179597794;179597793
N2A	4126	12601;12602;12603	chr2:178733068;178733067;178733066	chr2:179597795;179597794;179597793
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-37
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.7646
• 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
V/F	rs1560821296	None	0.003	N	0.211	0.172	0.457106177737	gnomAD-4.0.0	1.37176E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80253E-06	0	0
V/I	None	None	0.001	N	0.127	0.112	0.1749357433	gnomAD-4.0.0	2.05765E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80253E-06	1.16539E-05	0
V/L	None	None	0.001	N	0.097	0.112	0.128392430309	gnomAD-4.0.0	6.85882E-07	None	None	None	None	I	None	0	0	None	0	2.52934E-05	None	0	0	0	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
V/A	0.135	likely_benign	0.1367	benign	-0.829	Destabilizing	0.165	N	0.351	neutral	N	0.435929202	None	None	I
V/C	0.6937	likely_pathogenic	0.693	pathogenic	-0.662	Destabilizing	0.981	D	0.285	neutral	None	None	None	None	I
V/D	0.3329	likely_benign	0.3563	ambiguous	-0.512	Destabilizing	0.912	D	0.363	neutral	N	0.465292104	None	None	I
V/E	0.2127	likely_benign	0.2235	benign	-0.611	Destabilizing	0.818	D	0.353	neutral	None	None	None	None	I
V/F	0.1446	likely_benign	0.1464	benign	-0.908	Destabilizing	0.003	N	0.211	neutral	N	0.457479767	None	None	I
V/G	0.1603	likely_benign	0.1678	benign	-1.009	Destabilizing	0.773	D	0.357	neutral	N	0.472710413	None	None	I
V/H	0.503	ambiguous	0.5193	ambiguous	-0.499	Destabilizing	0.981	D	0.343	neutral	None	None	None	None	I
V/I	0.0722	likely_benign	0.072	benign	-0.489	Destabilizing	0.001	N	0.127	neutral	N	0.445666193	None	None	I
V/K	0.2319	likely_benign	0.243	benign	-0.663	Destabilizing	0.818	D	0.349	neutral	None	None	None	None	I
V/L	0.1272	likely_benign	0.1241	benign	-0.489	Destabilizing	0.001	N	0.097	neutral	N	0.457632626	None	None	I
V/M	0.115	likely_benign	0.1143	benign	-0.397	Destabilizing	0.69	D	0.285	neutral	None	None	None	None	I
V/N	0.2475	likely_benign	0.2586	benign	-0.352	Destabilizing	0.932	D	0.349	neutral	None	None	None	None	I
V/P	0.3404	ambiguous	0.3671	ambiguous	-0.566	Destabilizing	0.932	D	0.339	neutral	None	None	None	None	I
V/Q	0.2317	likely_benign	0.2359	benign	-0.623	Destabilizing	0.932	D	0.333	neutral	None	None	None	None	I
V/R	0.2002	likely_benign	0.2074	benign	-0.075	Destabilizing	0.818	D	0.349	neutral	None	None	None	None	I
V/S	0.1802	likely_benign	0.1863	benign	-0.769	Destabilizing	0.818	D	0.353	neutral	None	None	None	None	I
V/T	0.1813	likely_benign	0.1843	benign	-0.768	Destabilizing	0.388	N	0.293	neutral	None	None	None	None	I
V/W	0.6561	likely_pathogenic	0.6753	pathogenic	-0.968	Destabilizing	0.981	D	0.384	neutral	None	None	None	None	I
V/Y	0.4515	ambiguous	0.461	ambiguous	-0.689	Destabilizing	0.527	D	0.302	neutral	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.