TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8554	25885;25886;25887	chr2:178715754;178715753;178715752	chr2:179580481;179580480;179580479
N2AB	8237	24934;24935;24936	chr2:178715754;178715753;178715752	chr2:179580481;179580480;179580479
N2A	7310	22153;22154;22155	chr2:178715754;178715753;178715752	chr2:179580481;179580480;179580479
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-71
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5753
• 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
K/E	rs201945791	0.537	0.992	N	0.649	0.259	None	gnomAD-2.1.1	1.15357E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.38E-05	2.05991E-04	7.92644E-04
K/E	rs201945791	0.537	0.992	N	0.649	0.259	None	gnomAD-3.1.2	1.11732E-04	None	None	None	None	N	None	0	0	0	2.88184E-04	0	None	3.76648E-04	0	1.76424E-04	0	0
K/E	rs201945791	0.537	0.992	N	0.649	0.259	None	gnomAD-4.0.0	8.32718E-05	None	None	None	None	N	None	0	0	None	6.88089E-05	2.27967E-05	None	2.88785E-04	0	9.27845E-05	0	4.88647E-05
K/N	rs568546539	0.053	0.999	N	0.733	0.238	0.152612264143	gnomAD-2.1.1	4.92E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.83054E-04	None	0	0	0
K/N	rs568546539	0.053	0.999	N	0.733	0.238	0.152612264143	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	6.22148E-04	0
K/N	rs568546539	0.053	0.999	N	0.733	0.238	0.152612264143	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	2E-03	None
K/N	rs568546539	0.053	0.999	N	0.733	0.238	0.152612264143	gnomAD-4.0.0	1.26109E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.28556E-04	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
K/A	0.8425	likely_pathogenic	0.8279	pathogenic	-0.353	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
K/C	0.9584	likely_pathogenic	0.9509	pathogenic	-0.47	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/D	0.9161	likely_pathogenic	0.9077	pathogenic	0.495	Stabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
K/E	0.7339	likely_pathogenic	0.7114	pathogenic	0.574	Stabilizing	0.992	D	0.649	neutral	N	0.510445604	None	None	N
K/F	0.9538	likely_pathogenic	0.9483	pathogenic	-0.241	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
K/G	0.8605	likely_pathogenic	0.8527	pathogenic	-0.639	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/H	0.6232	likely_pathogenic	0.6003	pathogenic	-0.758	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/I	0.788	likely_pathogenic	0.7576	pathogenic	0.353	Stabilizing	0.982	D	0.789	deleterious	None	None	None	None	N
K/L	0.7602	likely_pathogenic	0.7387	pathogenic	0.353	Stabilizing	0.982	D	0.715	prob.delet.	None	None	None	None	N
K/M	0.6115	likely_pathogenic	0.5854	pathogenic	0.05	Stabilizing	0.998	D	0.714	prob.delet.	N	0.488243774	None	None	N
K/N	0.8144	likely_pathogenic	0.8034	pathogenic	-0.009	Destabilizing	0.999	D	0.733	prob.delet.	N	0.453917687	None	None	N
K/P	0.7983	likely_pathogenic	0.7923	pathogenic	0.147	Stabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
K/Q	0.4117	ambiguous	0.3966	ambiguous	-0.075	Destabilizing	0.994	D	0.705	prob.neutral	N	0.455047004	None	None	N
K/R	0.1258	likely_benign	0.1201	benign	-0.118	Destabilizing	0.987	D	0.581	neutral	N	0.472620721	None	None	N
K/S	0.875	likely_pathogenic	0.8654	pathogenic	-0.696	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
K/T	0.6418	likely_pathogenic	0.6133	pathogenic	-0.424	Destabilizing	0.998	D	0.775	deleterious	N	0.456199093	None	None	N
K/V	0.7694	likely_pathogenic	0.7389	pathogenic	0.147	Stabilizing	0.987	D	0.777	deleterious	None	None	None	None	N
K/W	0.9402	likely_pathogenic	0.9319	pathogenic	-0.145	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Y	0.8646	likely_pathogenic	0.852	pathogenic	0.161	Stabilizing	0.997	D	0.763	deleterious	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.