TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31067	93424;93425;93426	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
N2AB	29426	88501;88502;88503	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
N2A	28499	85720;85721;85722	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
N2B	22002	66229;66230;66231	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
Novex-1	22127	66604;66605;66606	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
Novex-2	22194	66805;66806;66807	chr2:178548427;178548426;178548425	chr2:179413154;179413153;179413152
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-114
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1552
• 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/T	rs373173796	None	0.896	N	0.501	0.152	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/T	rs373173796	None	0.896	N	0.501	0.152	None	gnomAD-4.0.0	6.57289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-05	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	0.0832	likely_benign	0.0896	benign	-0.499	Destabilizing	0.825	D	0.46	neutral	None	None	None	None	N
S/C	0.0914	likely_benign	0.0918	benign	-0.37	Destabilizing	0.999	D	0.633	neutral	N	0.517252225	None	None	N
S/D	0.4783	ambiguous	0.4964	ambiguous	-0.086	Destabilizing	0.851	D	0.566	neutral	None	None	None	None	N
S/E	0.6365	likely_pathogenic	0.6574	pathogenic	-0.018	Destabilizing	0.919	D	0.566	neutral	None	None	None	None	N
S/F	0.3109	likely_benign	0.3498	ambiguous	-0.594	Destabilizing	0.988	D	0.655	neutral	None	None	None	None	N
S/G	0.1007	likely_benign	0.0976	benign	-0.808	Destabilizing	0.811	D	0.502	neutral	N	0.488892187	None	None	N
S/H	0.3885	ambiguous	0.3996	ambiguous	-1.241	Destabilizing	0.997	D	0.634	neutral	None	None	None	None	N
S/I	0.2188	likely_benign	0.2453	benign	0.225	Stabilizing	0.811	D	0.565	neutral	N	0.517308153	None	None	N
S/K	0.7755	likely_pathogenic	0.7923	pathogenic	-0.358	Destabilizing	0.919	D	0.573	neutral	None	None	None	None	N
S/L	0.1223	likely_benign	0.1345	benign	0.225	Stabilizing	0.851	D	0.539	neutral	None	None	None	None	N
S/M	0.2048	likely_benign	0.2149	benign	0.173	Stabilizing	0.997	D	0.635	neutral	None	None	None	None	N
S/N	0.1543	likely_benign	0.161	benign	-0.589	Destabilizing	0.026	N	0.315	neutral	N	0.448504215	None	None	N
S/P	0.7781	likely_pathogenic	0.7658	pathogenic	0.02	Stabilizing	0.996	D	0.635	neutral	None	None	None	None	N
S/Q	0.5673	likely_pathogenic	0.5735	pathogenic	-0.528	Destabilizing	0.988	D	0.627	neutral	None	None	None	None	N
S/R	0.7211	likely_pathogenic	0.7308	pathogenic	-0.481	Destabilizing	0.968	D	0.629	neutral	D	0.523330048	None	None	N
S/T	0.0739	likely_benign	0.0765	benign	-0.483	Destabilizing	0.896	D	0.501	neutral	N	0.402193136	None	None	N
S/V	0.1997	likely_benign	0.2194	benign	0.02	Stabilizing	0.261	N	0.381	neutral	None	None	None	None	N
S/W	0.447	ambiguous	0.4855	ambiguous	-0.703	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
S/Y	0.2545	likely_benign	0.2772	benign	-0.33	Destabilizing	0.996	D	0.655	neutral	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.