TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9006	27241;27242;27243	chr2:178713118;178713117;178713116	chr2:179577845;179577844;179577843
N2AB	8689	26290;26291;26292	chr2:178713118;178713117;178713116	chr2:179577845;179577844;179577843
N2A	7762	23509;23510;23511	chr2:178713118;178713117;178713116	chr2:179577845;179577844;179577843
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-75
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.3904
• Predicted PPI site: I

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
S/F	None	None	0.035	N	0.385	0.318	0.630674063255	gnomAD-4.0.0	1.59165E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85873E-06	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
S/A	0.1024	likely_benign	0.1073	benign	-0.511	Destabilizing	0.826	D	0.327	neutral	N	0.496810742	None	None	I
S/C	0.1781	likely_benign	0.1651	benign	-0.378	Destabilizing	0.999	D	0.467	neutral	N	0.510966742	None	None	I
S/D	0.3589	ambiguous	0.3959	ambiguous	-0.142	Destabilizing	0.969	D	0.371	neutral	None	None	None	None	I
S/E	0.3955	ambiguous	0.4095	ambiguous	-0.225	Destabilizing	0.969	D	0.331	neutral	None	None	None	None	I
S/F	0.1904	likely_benign	0.1872	benign	-0.997	Destabilizing	0.035	N	0.385	neutral	N	0.501750031	None	None	I
S/G	0.1287	likely_benign	0.1386	benign	-0.652	Destabilizing	0.969	D	0.315	neutral	None	None	None	None	I
S/H	0.2606	likely_benign	0.2576	benign	-1.163	Destabilizing	0.999	D	0.47	neutral	None	None	None	None	I
S/I	0.1921	likely_benign	0.1982	benign	-0.262	Destabilizing	0.939	D	0.536	neutral	None	None	None	None	I
S/K	0.3893	ambiguous	0.4131	ambiguous	-0.666	Destabilizing	0.939	D	0.347	neutral	None	None	None	None	I
S/L	0.1344	likely_benign	0.1351	benign	-0.262	Destabilizing	0.884	D	0.509	neutral	None	None	None	None	I
S/M	0.2123	likely_benign	0.2105	benign	0.082	Stabilizing	0.997	D	0.472	neutral	None	None	None	None	I
S/N	0.13	likely_benign	0.14	benign	-0.42	Destabilizing	0.969	D	0.417	neutral	None	None	None	None	I
S/P	0.7857	likely_pathogenic	0.7908	pathogenic	-0.315	Destabilizing	0.996	D	0.455	neutral	N	0.501496541	None	None	I
S/Q	0.3487	ambiguous	0.3559	ambiguous	-0.709	Destabilizing	0.997	D	0.429	neutral	None	None	None	None	I
S/R	0.294	likely_benign	0.3118	benign	-0.4	Destabilizing	0.991	D	0.469	neutral	None	None	None	None	I
S/T	0.0823	likely_benign	0.0832	benign	-0.516	Destabilizing	0.061	N	0.137	neutral	N	0.458735144	None	None	I
S/V	0.2075	likely_benign	0.211	benign	-0.315	Destabilizing	0.939	D	0.531	neutral	None	None	None	None	I
S/W	0.3386	likely_benign	0.3303	benign	-0.964	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	I
S/Y	0.1756	likely_benign	0.1735	benign	-0.713	Destabilizing	0.953	D	0.56	neutral	N	0.499356948	None	None	I

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.