TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28101	84526;84527;84528	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
N2AB	26460	79603;79604;79605	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
N2A	25533	76822;76823;76824	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
N2B	19036	57331;57332;57333	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
Novex-1	19161	57706;57707;57708	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
Novex-2	19228	57907;57908;57909	chr2:178561831;178561830;178561829	chr2:179426558;179426557;179426556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-92
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5194
• 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
T/I	rs1483336920	-0.047	0.379	N	0.293	0.17	None	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs1483336920	-0.047	0.379	N	0.293	0.17	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/I	rs1483336920	-0.047	0.379	N	0.293	0.17	None	gnomAD-4.0.0	6.40658E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.19657E-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
T/A	0.0663	likely_benign	0.0656	benign	-0.56	Destabilizing	0.002	N	0.135	neutral	N	0.437556503	None	None	I
T/C	0.3665	ambiguous	0.341	ambiguous	-0.246	Destabilizing	0.977	D	0.315	neutral	None	None	None	None	I
T/D	0.292	likely_benign	0.2277	benign	0.123	Stabilizing	0.447	N	0.313	neutral	None	None	None	None	I
T/E	0.2579	likely_benign	0.1954	benign	0.065	Stabilizing	0.005	N	0.26	neutral	None	None	None	None	I
T/F	0.2203	likely_benign	0.2025	benign	-0.915	Destabilizing	0.92	D	0.372	neutral	None	None	None	None	I
T/G	0.1874	likely_benign	0.1762	benign	-0.726	Destabilizing	0.447	N	0.331	neutral	None	None	None	None	I
T/H	0.2276	likely_benign	0.1968	benign	-0.912	Destabilizing	0.977	D	0.379	neutral	None	None	None	None	I
T/I	0.1231	likely_benign	0.1082	benign	-0.229	Destabilizing	0.379	N	0.293	neutral	N	0.502877418	None	None	I
T/K	0.2047	likely_benign	0.159	benign	-0.483	Destabilizing	0.379	N	0.313	neutral	N	0.437036428	None	None	I
T/L	0.0907	likely_benign	0.0868	benign	-0.229	Destabilizing	0.447	N	0.303	neutral	None	None	None	None	I
T/M	0.092	likely_benign	0.0913	benign	-0.06	Destabilizing	0.92	D	0.3	neutral	None	None	None	None	I
T/N	0.0946	likely_benign	0.09	benign	-0.21	Destabilizing	0.85	D	0.279	neutral	None	None	None	None	I
T/P	0.2782	likely_benign	0.2359	benign	-0.31	Destabilizing	0.896	D	0.309	neutral	N	0.491948348	None	None	I
T/Q	0.2007	likely_benign	0.1708	benign	-0.417	Destabilizing	0.739	D	0.315	neutral	None	None	None	None	I
T/R	0.1755	likely_benign	0.1391	benign	-0.159	Destabilizing	0.81	D	0.311	neutral	N	0.464223029	None	None	I
T/S	0.0873	likely_benign	0.0862	benign	-0.457	Destabilizing	0.045	N	0.209	neutral	N	0.449021504	None	None	I
T/V	0.1001	likely_benign	0.0888	benign	-0.31	Destabilizing	0.005	N	0.204	neutral	None	None	None	None	I
T/W	0.6176	likely_pathogenic	0.5512	ambiguous	-0.899	Destabilizing	0.992	D	0.499	neutral	None	None	None	None	I
T/Y	0.2562	likely_benign	0.2284	benign	-0.651	Destabilizing	0.972	D	0.379	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.