TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32927	99004;99005;99006	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
N2AB	31286	94081;94082;94083	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
N2A	30359	91300;91301;91302	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
N2B	23862	71809;71810;71811	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
Novex-1	23987	72184;72185;72186	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
Novex-2	24054	72385;72386;72387	chr2:178539156;178539155;178539154	chr2:179403883;179403882;179403881
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: Fn3-128
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.2064
• 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
S/C	rs1559083914	None	1.0	N	0.795	0.476	0.451213972277	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/C	rs1559083914	None	1.0	N	0.795	0.476	0.451213972277	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31873E-05	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	0.1502	likely_benign	0.1363	benign	-0.417	Destabilizing	0.997	D	0.606	neutral	N	0.515171925	None	None	N
S/C	0.1478	likely_benign	0.1793	benign	-0.386	Destabilizing	1.0	D	0.795	deleterious	N	0.480766988	None	None	N
S/D	0.9572	likely_pathogenic	0.9372	pathogenic	-1.003	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
S/E	0.9537	likely_pathogenic	0.9462	pathogenic	-1.053	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
S/F	0.7185	likely_pathogenic	0.7183	pathogenic	-0.963	Destabilizing	1.0	D	0.82	deleterious	D	0.525863041	None	None	N
S/G	0.3599	ambiguous	0.2742	benign	-0.583	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
S/H	0.7984	likely_pathogenic	0.8074	pathogenic	-1.218	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/I	0.7611	likely_pathogenic	0.8012	pathogenic	-0.096	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
S/K	0.9729	likely_pathogenic	0.9745	pathogenic	-0.663	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
S/L	0.3767	ambiguous	0.3826	ambiguous	-0.096	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/M	0.6024	likely_pathogenic	0.6074	pathogenic	0.427	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
S/N	0.6565	likely_pathogenic	0.6168	pathogenic	-0.677	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
S/P	0.9913	likely_pathogenic	0.9933	pathogenic	-0.173	Destabilizing	1.0	D	0.828	deleterious	D	0.537130441	None	None	N
S/Q	0.8714	likely_pathogenic	0.8716	pathogenic	-1.017	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
S/R	0.9506	likely_pathogenic	0.9532	pathogenic	-0.385	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
S/T	0.3329	likely_benign	0.3087	benign	-0.603	Destabilizing	0.999	D	0.631	neutral	N	0.479246051	None	None	N
S/V	0.6461	likely_pathogenic	0.677	pathogenic	-0.173	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
S/W	0.8487	likely_pathogenic	0.8451	pathogenic	-0.991	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/Y	0.6546	likely_pathogenic	0.6656	pathogenic	-0.673	Destabilizing	1.0	D	0.825	deleterious	D	0.525609552	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.