TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27159	81700;81701;81702	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
N2AB	25518	76777;76778;76779	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
N2A	24591	73996;73997;73998	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
N2B	18094	54505;54506;54507	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
Novex-1	18219	54880;54881;54882	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
Novex-2	18286	55081;55082;55083	chr2:178564657;178564656;178564655	chr2:179429384;179429383;179429382
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: Fn3-85
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1592
• 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/R	None	None	0.983	D	0.853	0.722	0.59634542923	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
S/T	rs1173082517	-0.713	0.892	D	0.826	0.545	0.367042808489	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	1.14705E-04	0	None	0	0	None	0	None	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
S/A	0.4652	ambiguous	0.4472	ambiguous	-0.706	Destabilizing	0.818	D	0.809	deleterious	None	None	None	None	I
S/C	0.5739	likely_pathogenic	0.5734	pathogenic	-0.82	Destabilizing	0.999	D	0.823	deleterious	D	0.557511735	None	None	I
S/D	0.9956	likely_pathogenic	0.9954	pathogenic	-1.452	Destabilizing	0.957	D	0.851	deleterious	None	None	None	None	I
S/E	0.9963	likely_pathogenic	0.9961	pathogenic	-1.375	Destabilizing	0.916	D	0.841	deleterious	None	None	None	None	I
S/F	0.9959	likely_pathogenic	0.9948	pathogenic	-0.615	Destabilizing	0.996	D	0.902	deleterious	None	None	None	None	I
S/G	0.3846	ambiguous	0.4055	ambiguous	-1.012	Destabilizing	0.892	D	0.809	deleterious	D	0.531303178	None	None	I
S/H	0.9937	likely_pathogenic	0.9932	pathogenic	-1.446	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	I
S/I	0.9868	likely_pathogenic	0.9836	pathogenic	0.023	Stabilizing	0.983	D	0.897	deleterious	D	0.568525646	None	None	I
S/K	0.9993	likely_pathogenic	0.9992	pathogenic	-0.915	Destabilizing	0.916	D	0.848	deleterious	None	None	None	None	I
S/L	0.9469	likely_pathogenic	0.9342	pathogenic	0.023	Stabilizing	0.975	D	0.874	deleterious	None	None	None	None	I
S/M	0.9763	likely_pathogenic	0.972	pathogenic	0.109	Stabilizing	0.999	D	0.83	deleterious	None	None	None	None	I
S/N	0.9748	likely_pathogenic	0.9708	pathogenic	-1.218	Destabilizing	0.944	D	0.851	deleterious	D	0.568272156	None	None	I
S/P	0.9921	likely_pathogenic	0.991	pathogenic	-0.186	Destabilizing	0.033	N	0.688	prob.neutral	None	None	None	None	I
S/Q	0.9936	likely_pathogenic	0.993	pathogenic	-1.266	Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	I
S/R	0.9981	likely_pathogenic	0.9979	pathogenic	-0.903	Destabilizing	0.983	D	0.853	deleterious	D	0.549407433	None	None	I
S/T	0.6284	likely_pathogenic	0.6178	pathogenic	-0.997	Destabilizing	0.892	D	0.826	deleterious	D	0.536112116	None	None	I
S/V	0.9566	likely_pathogenic	0.9473	pathogenic	-0.186	Destabilizing	0.987	D	0.864	deleterious	None	None	None	None	I
S/W	0.9963	likely_pathogenic	0.9955	pathogenic	-0.743	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	I
S/Y	0.9944	likely_pathogenic	0.9932	pathogenic	-0.407	Destabilizing	0.996	D	0.901	deleterious	None	None	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.