TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31004	93235;93236;93237	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
N2AB	29363	88312;88313;88314	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
N2A	28436	85531;85532;85533	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
N2B	21939	66040;66041;66042	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
Novex-1	22064	66415;66416;66417	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
Novex-2	22131	66616;66617;66618	chr2:178548616;178548615;178548614	chr2:179413343;179413342;179413341
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: Ig-150
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.4493
• 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/N	rs762024916	0.154	0.055	D	0.279	0.109	0.170165803431	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.63388E-04	None	0	0	0
S/N	rs762024916	0.154	0.055	D	0.279	0.109	0.170165803431	gnomAD-4.0.0	7.52596E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-04	1.65662E-05

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	0.0897	likely_benign	0.0856	benign	-0.317	Destabilizing	0.007	N	0.293	neutral	None	None	None	None	I
S/C	0.0774	likely_benign	0.0732	benign	-0.246	Destabilizing	0.612	D	0.43	neutral	N	0.492039567	None	None	I
S/D	0.3908	ambiguous	0.3814	ambiguous	0.055	Stabilizing	0.072	N	0.268	neutral	None	None	None	None	I
S/E	0.334	likely_benign	0.3443	ambiguous	-0.056	Destabilizing	0.016	N	0.283	neutral	None	None	None	None	I
S/F	0.1982	likely_benign	0.1967	benign	-1.016	Destabilizing	0.356	N	0.511	neutral	None	None	None	None	I
S/G	0.097	likely_benign	0.0928	benign	-0.384	Destabilizing	0.024	N	0.28	neutral	N	0.502381914	None	None	I
S/H	0.1905	likely_benign	0.1973	benign	-0.928	Destabilizing	0.356	N	0.427	neutral	None	None	None	None	I
S/I	0.1154	likely_benign	0.1194	benign	-0.272	Destabilizing	0.093	N	0.515	neutral	D	0.524325418	None	None	I
S/K	0.2342	likely_benign	0.2627	benign	-0.405	Destabilizing	None	N	0.221	neutral	None	None	None	None	I
S/L	0.1011	likely_benign	0.1005	benign	-0.272	Destabilizing	0.038	N	0.469	neutral	None	None	None	None	I
S/M	0.1397	likely_benign	0.1425	benign	0.016	Stabilizing	0.356	N	0.421	neutral	None	None	None	None	I
S/N	0.1034	likely_benign	0.101	benign	-0.117	Destabilizing	0.055	N	0.279	neutral	D	0.529827238	None	None	I
S/P	0.5931	likely_pathogenic	0.5948	pathogenic	-0.261	Destabilizing	0.136	N	0.428	neutral	None	None	None	None	I
S/Q	0.2222	likely_benign	0.2289	benign	-0.403	Destabilizing	0.038	N	0.318	neutral	None	None	None	None	I
S/R	0.2217	likely_benign	0.2407	benign	-0.204	Destabilizing	None	N	0.25	neutral	N	0.484766952	None	None	I
S/T	0.0676	likely_benign	0.067	benign	-0.231	Destabilizing	None	N	0.219	neutral	N	0.467893345	None	None	I
S/V	0.1359	likely_benign	0.1312	benign	-0.261	Destabilizing	0.038	N	0.479	neutral	None	None	None	None	I
S/W	0.3382	likely_benign	0.3459	ambiguous	-1.037	Destabilizing	0.864	D	0.544	neutral	None	None	None	None	I
S/Y	0.185	likely_benign	0.1852	benign	-0.748	Destabilizing	0.356	N	0.512	neutral	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.