TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8635	26128;26129;26130	chr2:178715511;178715510;178715509	chr2:179580238;179580237;179580236
N2AB	8318	25177;25178;25179	chr2:178715511;178715510;178715509	chr2:179580238;179580237;179580236
N2A	7391	22396;22397;22398	chr2:178715511;178715510;178715509	chr2:179580238;179580237;179580236
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-71
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.0768
• 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
T/A	None	None	0.934	N	0.572	0.154	0.220303561663	gnomAD-4.0.0	1.20039E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-06	0	0
T/I	rs1005082166	None	1.0	N	0.825	0.315	0.475192790171	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1005082166	None	1.0	N	0.825	0.315	0.475192790171	gnomAD-4.0.0	1.24085E-06	None	None	None	None	N	None	1.33636E-05	0	None	0	0	None	0	0	8.48675E-07	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
T/A	0.0927	likely_benign	0.0875	benign	-1.395	Destabilizing	0.934	D	0.572	neutral	N	0.4478005	None	None	N
T/C	0.4992	ambiguous	0.4896	ambiguous	-1.437	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/D	0.9154	likely_pathogenic	0.8708	pathogenic	-1.484	Destabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
T/E	0.897	likely_pathogenic	0.8579	pathogenic	-1.333	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/F	0.5068	ambiguous	0.4789	ambiguous	-1.558	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
T/G	0.4416	ambiguous	0.3745	ambiguous	-1.723	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
T/H	0.7408	likely_pathogenic	0.6974	pathogenic	-1.945	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/I	0.2262	likely_benign	0.2438	benign	-0.555	Destabilizing	1.0	D	0.825	deleterious	N	0.50515808	None	None	N
T/K	0.8485	likely_pathogenic	0.7895	pathogenic	-0.682	Destabilizing	1.0	D	0.781	deleterious	N	0.513622861	None	None	N
T/L	0.1872	likely_benign	0.1821	benign	-0.555	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
T/M	0.145	likely_benign	0.15	benign	-0.402	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
T/N	0.451	ambiguous	0.4141	ambiguous	-1.299	Destabilizing	0.997	D	0.719	prob.delet.	None	None	None	None	N
T/P	0.7661	likely_pathogenic	0.702	pathogenic	-0.807	Destabilizing	0.999	D	0.827	deleterious	D	0.525232656	None	None	N
T/Q	0.7596	likely_pathogenic	0.7033	pathogenic	-1.261	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
T/R	0.7365	likely_pathogenic	0.6665	pathogenic	-0.727	Destabilizing	1.0	D	0.838	deleterious	N	0.513622861	None	None	N
T/S	0.1939	likely_benign	0.1734	benign	-1.583	Destabilizing	0.51	D	0.386	neutral	N	0.471605654	None	None	N
T/V	0.166	likely_benign	0.175	benign	-0.807	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
T/W	0.9112	likely_pathogenic	0.8949	pathogenic	-1.554	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
T/Y	0.6946	likely_pathogenic	0.6681	pathogenic	-1.205	Destabilizing	1.0	D	0.86	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.