TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19940	60043;60044;60045	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
N2AB	18299	55120;55121;55122	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
N2A	17372	52339;52340;52341	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
N2B	10875	32848;32849;32850	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
Novex-1	11000	33223;33224;33225	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
Novex-2	11067	33424;33425;33426	chr2:178592086;178592085;178592084	chr2:179456813;179456812;179456811
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-32
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.8379
• 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
H/Q	None	None	0.995	N	0.461	0.185	0.262662153117	gnomAD-4.0.0	5.47618E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29764E-06	0	1.65777E-05
H/Y	rs192279089	0.99	0.026	N	0.181	0.137	0.1749357433	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
H/Y	rs192279089	0.99	0.026	N	0.181	0.137	0.1749357433	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Y	rs192279089	0.99	0.026	N	0.181	0.137	0.1749357433	gnomAD-4.0.0	8.06018E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.10216E-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
H/A	0.2491	likely_benign	0.2522	benign	0.399	Stabilizing	0.919	D	0.449	neutral	None	None	None	None	N
H/C	0.2003	likely_benign	0.186	benign	0.649	Stabilizing	0.999	D	0.639	neutral	None	None	None	None	N
H/D	0.1881	likely_benign	0.2133	benign	-0.034	Destabilizing	0.995	D	0.475	neutral	N	0.400069976	None	None	N
H/E	0.3269	likely_benign	0.341	ambiguous	-0.029	Destabilizing	0.959	D	0.436	neutral	None	None	None	None	N
H/F	0.1608	likely_benign	0.149	benign	0.908	Stabilizing	0.952	D	0.456	neutral	None	None	None	None	N
H/G	0.2104	likely_benign	0.2217	benign	0.165	Stabilizing	0.959	D	0.46	neutral	None	None	None	None	N
H/I	0.297	likely_benign	0.2794	benign	0.975	Stabilizing	0.976	D	0.599	neutral	None	None	None	None	N
H/K	0.3033	likely_benign	0.3429	ambiguous	0.347	Stabilizing	0.988	D	0.455	neutral	None	None	None	None	N
H/L	0.1308	likely_benign	0.1236	benign	0.975	Stabilizing	0.811	D	0.52	neutral	N	0.465818468	None	None	N
H/M	0.3614	ambiguous	0.3531	ambiguous	0.706	Stabilizing	0.999	D	0.55	neutral	None	None	None	None	N
H/N	0.0692	likely_benign	0.0734	benign	0.302	Stabilizing	0.946	D	0.465	neutral	N	0.377635834	None	None	N
H/P	0.279	likely_benign	0.2696	benign	0.808	Stabilizing	0.995	D	0.545	neutral	N	0.480400416	None	None	N
H/Q	0.1944	likely_benign	0.2007	benign	0.357	Stabilizing	0.995	D	0.461	neutral	N	0.480227058	None	None	N
H/R	0.175	likely_benign	0.1923	benign	-0.126	Destabilizing	0.984	D	0.464	neutral	N	0.433185259	None	None	N
H/S	0.1901	likely_benign	0.1937	benign	0.387	Stabilizing	0.959	D	0.449	neutral	None	None	None	None	N
H/T	0.2276	likely_benign	0.2288	benign	0.486	Stabilizing	0.988	D	0.492	neutral	None	None	None	None	N
H/V	0.2476	likely_benign	0.2379	benign	0.808	Stabilizing	0.976	D	0.542	neutral	None	None	None	None	N
H/W	0.3394	likely_benign	0.3325	benign	0.827	Stabilizing	0.997	D	0.555	neutral	None	None	None	None	N
H/Y	0.0639	likely_benign	0.0597	benign	1.119	Stabilizing	0.026	N	0.181	neutral	N	0.424355132	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.