TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19228	57907;57908;57909	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
N2AB	17587	52984;52985;52986	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
N2A	16660	50203;50204;50205	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
N2B	10163	30712;30713;30714	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
Novex-1	10288	31087;31088;31089	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
Novex-2	10355	31288;31289;31290	chr2:178595672;178595671;178595670	chr2:179460399;179460398;179460397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-27
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.4414
• 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	rs757820671	-0.35	0.992	N	0.597	0.458	None	gnomAD-2.1.1	4.05E-05	None	None	None	None	N	None	1.70416E-04	1.15902E-04	None	0	0	None	0	None	0	2.42E-05	0
R/C	rs757820671	-0.35	0.992	N	0.597	0.458	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	N	None	1.45145E-04	6.56E-05	0	0	0	None	0	0	0	0	0
R/C	rs757820671	-0.35	0.992	N	0.597	0.458	None	gnomAD-4.0.0	1.67895E-05	None	None	None	None	N	None	1.73899E-04	5.05493E-05	None	0	0	None	0	0	6.79479E-06	1.11351E-05	3.21017E-05
R/H	rs114711705	-1.232	0.005	N	0.195	0.107	None	gnomAD-2.1.1	6.82103E-04	None	None	None	None	N	None	7.37866E-03	2.32194E-04	None	0	5.34E-05	None	0	None	0	0	4.3054E-04
R/H	rs114711705	-1.232	0.005	N	0.195	0.107	None	gnomAD-3.1.2	1.96786E-03	None	None	None	None	N	None	7.05484E-03	1.31182E-04	0	0	1.9425E-04	None	0	0	0	0	1.91205E-03
R/H	rs114711705	-1.232	0.005	N	0.195	0.107	None	1000 genomes	2.59585E-03	None	None	None	None	N	None	9.8E-03	0	None	None	0	0	None	None	None	0	None
R/H	rs114711705	-1.232	0.005	N	0.195	0.107	None	gnomAD-4.0.0	3.97341E-04	None	None	None	None	N	None	7.6999E-03	3.03306E-04	None	0	2.25063E-05	None	1.56966E-05	0	6.79519E-06	1.11421E-05	5.29593E-04

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	0.6822	likely_pathogenic	0.7887	pathogenic	-0.3	Destabilizing	0.272	N	0.385	neutral	None	None	None	None	N
R/C	0.1986	likely_benign	0.3258	benign	-0.245	Destabilizing	0.992	D	0.597	neutral	N	0.48673388	None	None	N
R/D	0.8702	likely_pathogenic	0.9307	pathogenic	-0.016	Destabilizing	0.567	D	0.393	neutral	None	None	None	None	N
R/E	0.631	likely_pathogenic	0.7667	pathogenic	0.064	Stabilizing	0.157	N	0.309	neutral	None	None	None	None	N
R/F	0.6931	likely_pathogenic	0.8115	pathogenic	-0.382	Destabilizing	0.567	D	0.503	neutral	None	None	None	None	N
R/G	0.3997	ambiguous	0.5889	pathogenic	-0.546	Destabilizing	0.417	N	0.368	neutral	N	0.487459675	None	None	N
R/H	0.1055	likely_benign	0.2433	benign	-0.976	Destabilizing	0.005	N	0.195	neutral	N	0.462842727	None	None	N
R/I	0.5936	likely_pathogenic	0.7048	pathogenic	0.33	Stabilizing	0.726	D	0.498	neutral	None	None	None	None	N
R/K	0.1676	likely_benign	0.2188	benign	-0.324	Destabilizing	0.133	N	0.359	neutral	None	None	None	None	N
R/L	0.4209	ambiguous	0.5555	ambiguous	0.33	Stabilizing	0.417	N	0.379	neutral	N	0.479478952	None	None	N
R/M	0.4684	ambiguous	0.6281	pathogenic	0.021	Stabilizing	0.968	D	0.348	neutral	None	None	None	None	N
R/N	0.7211	likely_pathogenic	0.836	pathogenic	0.131	Stabilizing	0.157	N	0.293	neutral	None	None	None	None	N
R/P	0.9571	likely_pathogenic	0.9688	pathogenic	0.142	Stabilizing	0.836	D	0.43	neutral	N	0.504546712	None	None	N
R/Q	0.1311	likely_benign	0.1849	benign	-0.05	Destabilizing	0.567	D	0.315	neutral	None	None	None	None	N
R/S	0.6947	likely_pathogenic	0.8106	pathogenic	-0.418	Destabilizing	0.417	N	0.351	neutral	N	0.449362646	None	None	N
R/T	0.5362	ambiguous	0.6917	pathogenic	-0.185	Destabilizing	0.567	D	0.336	neutral	None	None	None	None	N
R/V	0.66	likely_pathogenic	0.7565	pathogenic	0.142	Stabilizing	0.726	D	0.508	neutral	None	None	None	None	N
R/W	0.2859	likely_benign	0.4379	ambiguous	-0.256	Destabilizing	0.968	D	0.617	neutral	None	None	None	None	N
R/Y	0.5043	ambiguous	0.6727	pathogenic	0.106	Stabilizing	0.396	N	0.433	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.