TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28063	84412;84413;84414	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
N2AB	26422	79489;79490;79491	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
N2A	25495	76708;76709;76710	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
N2B	18998	57217;57218;57219	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
Novex-1	19123	57592;57593;57594	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
Novex-2	19190	57793;57794;57795	chr2:178561945;178561944;178561943	chr2:179426672;179426671;179426670
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: Fn3-92
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.7438
• 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
R/C	rs539595292	-0.098	0.964	N	0.408	0.148	0.424908009808	gnomAD-2.1.1	2.51E-05	None	None	None	None	N	None	4.13E-05	8.51E-05	None	0	0	None	0	None	0	2.35E-05	0
R/C	rs539595292	-0.098	0.964	N	0.408	0.148	0.424908009808	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs539595292	-0.098	0.964	N	0.408	0.148	0.424908009808	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/C	rs539595292	-0.098	0.964	N	0.408	0.148	0.424908009808	gnomAD-4.0.0	1.42571E-05	None	None	None	None	N	None	1.33312E-05	5.002E-05	None	0	0	None	0	0	1.44132E-05	1.0981E-05	1.60149E-05
R/H	rs570847832	-0.708	None	N	0.175	0.179	None	gnomAD-2.1.1	8.47E-05	None	None	None	None	N	None	1.29266E-04	0	None	0	5.61E-05	None	2.61626E-04	None	0	8.92E-05	0
R/H	rs570847832	-0.708	None	N	0.175	0.179	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	2.94E-05	0	4.78927E-04
R/H	rs570847832	-0.708	None	N	0.175	0.179	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/H	rs570847832	-0.708	None	N	0.175	0.179	None	gnomAD-4.0.0	6.13723E-05	None	None	None	None	N	None	3.99979E-05	0	None	0	0	None	0	0	7.03769E-05	8.78503E-05	8.00897E-05

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	0.2327	likely_benign	0.1986	benign	-0.542	Destabilizing	0.007	N	0.275	neutral	None	None	None	None	N
R/C	0.0856	likely_benign	0.0811	benign	-0.422	Destabilizing	0.964	D	0.408	neutral	N	0.469789076	None	None	N
R/D	0.3738	ambiguous	0.3206	benign	-0.001	Destabilizing	0.031	N	0.365	neutral	None	None	None	None	N
R/E	0.226	likely_benign	0.1893	benign	0.108	Stabilizing	0.007	N	0.245	neutral	None	None	None	None	N
R/F	0.2749	likely_benign	0.2506	benign	-0.49	Destabilizing	0.214	N	0.501	neutral	None	None	None	None	N
R/G	0.2039	likely_benign	0.1591	benign	-0.838	Destabilizing	0.03	N	0.328	neutral	N	0.476764062	None	None	N
R/H	0.0608	likely_benign	0.0613	benign	-1.277	Destabilizing	None	N	0.175	neutral	N	0.505493649	None	None	N
R/I	0.1377	likely_benign	0.1297	benign	0.24	Stabilizing	0.136	N	0.552	neutral	None	None	None	None	N
R/K	0.091	likely_benign	0.0787	benign	-0.562	Destabilizing	None	N	0.12	neutral	None	None	None	None	N
R/L	0.1327	likely_benign	0.1232	benign	0.24	Stabilizing	0.058	N	0.366	neutral	N	0.517654869	None	None	N
R/M	0.1924	likely_benign	0.1678	benign	-0.06	Destabilizing	0.356	N	0.475	neutral	None	None	None	None	N
R/N	0.2459	likely_benign	0.2218	benign	-0.03	Destabilizing	0.016	N	0.377	neutral	None	None	None	None	N
R/P	0.8145	likely_pathogenic	0.7127	pathogenic	0.001	Stabilizing	0.232	N	0.53	neutral	N	0.485918322	None	None	N
R/Q	0.0725	likely_benign	0.0703	benign	-0.198	Destabilizing	0.001	N	0.183	neutral	None	None	None	None	N
R/S	0.2344	likely_benign	0.2028	benign	-0.699	Destabilizing	0.001	N	0.2	neutral	N	0.45591019	None	None	N
R/T	0.1346	likely_benign	0.1203	benign	-0.414	Destabilizing	0.016	N	0.383	neutral	None	None	None	None	N
R/V	0.1613	likely_benign	0.159	benign	0.001	Stabilizing	0.072	N	0.46	neutral	None	None	None	None	N
R/W	0.1495	likely_benign	0.1302	benign	-0.239	Destabilizing	0.864	D	0.42	neutral	None	None	None	None	N
R/Y	0.1833	likely_benign	0.1639	benign	0.091	Stabilizing	0.038	N	0.555	neutral	None	None	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.