TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18637	56134;56135;56136	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
N2AB	16996	51211;51212;51213	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
N2A	16069	48430;48431;48432	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
N2B	9572	28939;28940;28941	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
Novex-1	9697	29314;29315;29316	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
Novex-2	9764	29515;29516;29517	chr2:178600995;178600994;178600993	chr2:179465722;179465721;179465720
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-23
• Domain position: 59
• Structural Position: 72
• Q(SASA): 0.7289
• 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
R/C	rs374151130	0.022	1.0	N	0.775	0.398	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/C	rs374151130	0.022	1.0	N	0.775	0.398	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs374151130	0.022	1.0	N	0.775	0.398	None	gnomAD-4.0.0	5.14614E-05	None	None	None	None	I	None	1.33661E-05	0	None	0	0	None	0	0	6.86819E-05	0	1.60174E-05
R/H	rs758627195	-0.615	1.0	N	0.779	0.386	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.81E-05	None	0	8.94E-06	0
R/H	rs758627195	-0.615	1.0	N	0.779	0.386	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	4.1425E-04	0
R/H	rs758627195	-0.615	1.0	N	0.779	0.386	None	gnomAD-4.0.0	1.79789E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54367E-06	2.74593E-04	1.60164E-05
R/L	rs758627195	None	1.0	N	0.633	0.46	0.45553875121	gnomAD-4.0.0	6.84463E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99742E-07	0	0
R/S	rs374151130	0.129	1.0	N	0.69	0.404	None	gnomAD-2.1.1	3.23E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	7.15E-05	0
R/S	rs374151130	0.129	1.0	N	0.69	0.404	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/S	rs374151130	0.129	1.0	N	0.69	0.404	None	gnomAD-4.0.0	1.48804E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.03502E-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
R/A	0.6405	likely_pathogenic	0.7046	pathogenic	0.079	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	I
R/C	0.4552	ambiguous	0.4648	ambiguous	-0.153	Destabilizing	1.0	D	0.775	deleterious	N	0.474002131	None	None	I
R/D	0.7706	likely_pathogenic	0.8149	pathogenic	-0.312	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
R/E	0.5161	ambiguous	0.542	ambiguous	-0.275	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	I
R/F	0.7862	likely_pathogenic	0.8033	pathogenic	-0.24	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/G	0.4265	ambiguous	0.5047	ambiguous	-0.054	Destabilizing	1.0	D	0.633	neutral	N	0.454083394	None	None	I
R/H	0.2171	likely_benign	0.2124	benign	-0.587	Destabilizing	1.0	D	0.779	deleterious	N	0.487811965	None	None	I
R/I	0.5256	ambiguous	0.5573	ambiguous	0.383	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
R/K	0.1723	likely_benign	0.178	benign	-0.092	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	I
R/L	0.5057	ambiguous	0.536	ambiguous	0.383	Stabilizing	1.0	D	0.633	neutral	N	0.475882818	None	None	I
R/M	0.4892	ambiguous	0.5369	ambiguous	-0.052	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
R/N	0.7073	likely_pathogenic	0.779	pathogenic	0.026	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
R/P	0.8864	likely_pathogenic	0.9255	pathogenic	0.299	Stabilizing	1.0	D	0.704	prob.neutral	N	0.483651365	None	None	I
R/Q	0.2036	likely_benign	0.2007	benign	-0.014	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
R/S	0.7191	likely_pathogenic	0.7817	pathogenic	-0.123	Destabilizing	1.0	D	0.69	prob.neutral	N	0.456678195	None	None	I
R/T	0.4637	ambiguous	0.5198	ambiguous	0.014	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
R/V	0.6163	likely_pathogenic	0.6385	pathogenic	0.299	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
R/W	0.3312	likely_benign	0.3472	ambiguous	-0.44	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
R/Y	0.5968	likely_pathogenic	0.6203	pathogenic	-0.037	Destabilizing	1.0	D	0.736	prob.delet.	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.