TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32190	96793;96794;96795	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
N2AB	30549	91870;91871;91872	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
N2A	29622	89089;89090;89091	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
N2B	23125	69598;69599;69600	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
Novex-1	23250	69973;69974;69975	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
Novex-2	23317	70174;70175;70176	chr2:178543405;178543404;178543403	chr2:179408132;179408131;179408130
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-122
• Domain position: 86
• Structural Position: 120
• Q(SASA): 0.3033
• 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
P/A	rs1314931381	-1.696	0.028	N	0.417	0.253	0.322230723748	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
P/A	rs1314931381	-1.696	0.028	N	0.417	0.253	0.322230723748	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	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
P/A	0.1321	likely_benign	0.1269	benign	-1.554	Destabilizing	0.028	N	0.417	neutral	N	0.476088818	None	None	N
P/C	0.8339	likely_pathogenic	0.8123	pathogenic	-0.83	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
P/D	0.9597	likely_pathogenic	0.9564	pathogenic	-1.566	Destabilizing	0.955	D	0.667	neutral	None	None	None	None	N
P/E	0.9098	likely_pathogenic	0.899	pathogenic	-1.605	Destabilizing	0.943	D	0.674	neutral	None	None	None	None	N
P/F	0.8726	likely_pathogenic	0.8349	pathogenic	-1.288	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
P/G	0.427	ambiguous	0.5092	ambiguous	-1.826	Destabilizing	0.087	N	0.469	neutral	None	None	None	None	N
P/H	0.7681	likely_pathogenic	0.725	pathogenic	-1.324	Destabilizing	1.0	D	0.724	prob.delet.	N	0.519440579	None	None	N
P/I	0.861	likely_pathogenic	0.8216	pathogenic	-0.909	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
P/K	0.9356	likely_pathogenic	0.9272	pathogenic	-1.366	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
P/L	0.6666	likely_pathogenic	0.5883	pathogenic	-0.909	Destabilizing	0.998	D	0.717	prob.delet.	N	0.499054918	None	None	N
P/M	0.8194	likely_pathogenic	0.7883	pathogenic	-0.575	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
P/N	0.8808	likely_pathogenic	0.8715	pathogenic	-1.032	Destabilizing	0.985	D	0.708	prob.delet.	None	None	None	None	N
P/Q	0.7451	likely_pathogenic	0.7327	pathogenic	-1.285	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
P/R	0.8665	likely_pathogenic	0.8357	pathogenic	-0.699	Destabilizing	0.999	D	0.715	prob.delet.	N	0.500322366	None	None	N
P/S	0.3794	ambiguous	0.3816	ambiguous	-1.454	Destabilizing	0.941	D	0.59	neutral	N	0.494953542	None	None	N
P/T	0.5272	ambiguous	0.4928	ambiguous	-1.404	Destabilizing	0.98	D	0.685	prob.neutral	N	0.500575855	None	None	N
P/V	0.7218	likely_pathogenic	0.6668	pathogenic	-1.091	Destabilizing	0.979	D	0.673	neutral	None	None	None	None	N
P/W	0.9553	likely_pathogenic	0.9379	pathogenic	-1.429	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
P/Y	0.8694	likely_pathogenic	0.8382	pathogenic	-1.202	Destabilizing	1.0	D	0.766	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.