TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7294	22105;22106;22107	chr2:178723127;178723126;178723125	chr2:179587854;179587853;179587852
N2AB	6977	21154;21155;21156	chr2:178723127;178723126;178723125	chr2:179587854;179587853;179587852
N2A	6050	18373;18374;18375	chr2:178723127;178723126;178723125	chr2:179587854;179587853;179587852
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-57
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.8372
• 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	rs1333823103	0.344	0.565	N	0.427	0.193	0.188950314367	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	8.71E-05	None	0	0	None	0	None	0	0	0
K/E	rs1333823103	0.344	0.565	N	0.427	0.193	0.188950314367	gnomAD-4.0.0	4.77528E-06	None	None	None	None	N	None	0	6.86185E-05	None	0	0	None	0	0	0	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
K/A	0.1828	likely_benign	0.186	benign	0.128	Stabilizing	0.633	D	0.416	neutral	None	None	None	None	N
K/C	0.6695	likely_pathogenic	0.6816	pathogenic	-0.072	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	N
K/D	0.2994	likely_benign	0.3138	benign	0.015	Stabilizing	0.923	D	0.357	neutral	None	None	None	None	N
K/E	0.0914	likely_benign	0.0972	benign	0.017	Stabilizing	0.565	D	0.427	neutral	N	0.456496475	None	None	N
K/F	0.5844	likely_pathogenic	0.5874	pathogenic	-0.101	Destabilizing	0.987	D	0.532	neutral	None	None	None	None	N
K/G	0.2471	likely_benign	0.2649	benign	-0.054	Destabilizing	0.775	D	0.381	neutral	None	None	None	None	N
K/H	0.2842	likely_benign	0.3099	benign	-0.289	Destabilizing	0.989	D	0.407	neutral	None	None	None	None	N
K/I	0.1992	likely_benign	0.2018	benign	0.528	Stabilizing	0.901	D	0.533	neutral	N	0.499844608	None	None	N
K/L	0.2217	likely_benign	0.2346	benign	0.528	Stabilizing	0.775	D	0.397	neutral	None	None	None	None	N
K/M	0.1709	likely_benign	0.1794	benign	0.213	Stabilizing	0.989	D	0.407	neutral	None	None	None	None	N
K/N	0.243	likely_benign	0.2511	benign	0.381	Stabilizing	0.901	D	0.36	neutral	N	0.486974098	None	None	N
K/P	0.3113	likely_benign	0.3173	benign	0.422	Stabilizing	0.961	D	0.403	neutral	None	None	None	None	N
K/Q	0.1039	likely_benign	0.1098	benign	0.228	Stabilizing	0.075	N	0.27	neutral	N	0.511235037	None	None	N
K/R	0.0772	likely_benign	0.0801	benign	0.055	Stabilizing	0.565	D	0.427	neutral	N	0.442969818	None	None	N
K/S	0.2173	likely_benign	0.2225	benign	-0.037	Destabilizing	0.633	D	0.411	neutral	None	None	None	None	N
K/T	0.1207	likely_benign	0.1277	benign	0.102	Stabilizing	0.034	N	0.33	neutral	N	0.483683077	None	None	N
K/V	0.187	likely_benign	0.1918	benign	0.422	Stabilizing	0.923	D	0.385	neutral	None	None	None	None	N
K/W	0.6492	likely_pathogenic	0.6698	pathogenic	-0.171	Destabilizing	0.996	D	0.6	neutral	None	None	None	None	N
K/Y	0.4747	ambiguous	0.4974	ambiguous	0.189	Stabilizing	0.961	D	0.476	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.