TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32984	99175;99176;99177	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
N2AB	31343	94252;94253;94254	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
N2A	30416	91471;91472;91473	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
N2B	23919	71980;71981;71982	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
Novex-1	24044	72355;72356;72357	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
Novex-2	24111	72556;72557;72558	chr2:178538985;178538984;178538983	chr2:179403712;179403711;179403710
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-128
• Domain position: 89
• Structural Position: 121
• Q(SASA): 0.1684
• 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/R	None	None	0.998	N	0.861	0.594	0.497152477365	gnomAD-4.0.0	6.84894E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00471E-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
S/A	0.3345	likely_benign	0.2959	benign	-0.759	Destabilizing	0.871	D	0.663	neutral	None	None	None	None	N
S/C	0.4198	ambiguous	0.3462	ambiguous	-0.825	Destabilizing	1.0	D	0.83	deleterious	D	0.545167925	None	None	N
S/D	0.9859	likely_pathogenic	0.9765	pathogenic	-1.642	Destabilizing	0.985	D	0.793	deleterious	None	None	None	None	N
S/E	0.9911	likely_pathogenic	0.9855	pathogenic	-1.535	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
S/F	0.9652	likely_pathogenic	0.9432	pathogenic	-0.6	Destabilizing	0.999	D	0.876	deleterious	None	None	None	None	N
S/G	0.2181	likely_benign	0.1824	benign	-1.086	Destabilizing	0.011	N	0.492	neutral	D	0.525848357	None	None	N
S/H	0.9668	likely_pathogenic	0.9473	pathogenic	-1.484	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
S/I	0.9011	likely_pathogenic	0.8398	pathogenic	0.038	Stabilizing	0.998	D	0.881	deleterious	D	0.526556691	None	None	N
S/K	0.9977	likely_pathogenic	0.9958	pathogenic	-0.854	Destabilizing	0.985	D	0.801	deleterious	None	None	None	None	N
S/L	0.7846	likely_pathogenic	0.7198	pathogenic	0.038	Stabilizing	0.985	D	0.865	deleterious	None	None	None	None	N
S/M	0.8824	likely_pathogenic	0.8474	pathogenic	0.078	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/N	0.8635	likely_pathogenic	0.8077	pathogenic	-1.269	Destabilizing	0.98	D	0.797	deleterious	D	0.544407456	None	None	N
S/P	0.9707	likely_pathogenic	0.9563	pathogenic	-0.194	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
S/Q	0.981	likely_pathogenic	0.9719	pathogenic	-1.247	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
S/R	0.9953	likely_pathogenic	0.9894	pathogenic	-0.912	Destabilizing	0.998	D	0.861	deleterious	N	0.507438478	None	None	N
S/T	0.3898	ambiguous	0.3534	ambiguous	-0.998	Destabilizing	0.98	D	0.794	deleterious	N	0.499574438	None	None	N
S/V	0.8624	likely_pathogenic	0.8048	pathogenic	-0.194	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
S/W	0.9799	likely_pathogenic	0.9639	pathogenic	-0.783	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
S/Y	0.9556	likely_pathogenic	0.9223	pathogenic	-0.418	Destabilizing	0.999	D	0.875	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.