TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25917	77974;77975;77976	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
N2AB	24276	73051;73052;73053	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
N2A	23349	70270;70271;70272	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
N2B	16852	50779;50780;50781	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
Novex-1	16977	51154;51155;51156	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
Novex-2	17044	51355;51356;51357	chr2:178568383;178568382;178568381	chr2:179433110;179433109;179433108
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-76
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.8094
• 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
Y/H	rs370137092	0.57	0.994	N	0.577	0.317	None	gnomAD-2.1.1	3.63E-05	None	None	None	None	I	None	0	5.82E-05	None	0	0	None	0	None	0	6.23E-05	0
Y/H	rs370137092	0.57	0.994	N	0.577	0.317	None	gnomAD-3.1.2	6.57E-05	None	None	None	None	I	None	0	1.9667E-04	0	0	0	None	0	0	1.02941E-04	0	0
Y/H	rs370137092	0.57	0.994	N	0.577	0.317	None	gnomAD-4.0.0	5.14524E-05	None	None	None	None	I	None	0	8.34585E-05	None	0	0	None	0	0	6.27354E-05	2.19602E-05	3.20431E-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
Y/A	0.7115	likely_pathogenic	0.7096	pathogenic	-0.906	Destabilizing	0.916	D	0.489	neutral	None	None	None	None	I
Y/C	0.2817	likely_benign	0.2678	benign	0.076	Stabilizing	0.999	D	0.655	neutral	N	0.507863102	None	None	I
Y/D	0.3684	ambiguous	0.4066	ambiguous	0.834	Stabilizing	0.025	N	0.489	neutral	N	0.418559737	None	None	I
Y/E	0.7293	likely_pathogenic	0.753	pathogenic	0.816	Stabilizing	0.845	D	0.487	neutral	None	None	None	None	I
Y/F	0.1071	likely_benign	0.1095	benign	-0.495	Destabilizing	0.981	D	0.535	neutral	N	0.509856532	None	None	I
Y/G	0.622	likely_pathogenic	0.6403	pathogenic	-1.106	Destabilizing	0.975	D	0.517	neutral	None	None	None	None	I
Y/H	0.2257	likely_benign	0.2354	benign	0.074	Stabilizing	0.994	D	0.577	neutral	N	0.515686426	None	None	I
Y/I	0.7104	likely_pathogenic	0.7103	pathogenic	-0.398	Destabilizing	0.987	D	0.579	neutral	None	None	None	None	I
Y/K	0.7603	likely_pathogenic	0.7624	pathogenic	0.125	Stabilizing	0.975	D	0.605	neutral	None	None	None	None	I
Y/L	0.6078	likely_pathogenic	0.6002	pathogenic	-0.398	Destabilizing	0.957	D	0.557	neutral	None	None	None	None	I
Y/M	0.7703	likely_pathogenic	0.76	pathogenic	-0.119	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	I
Y/N	0.1974	likely_benign	0.2171	benign	-0.014	Destabilizing	0.935	D	0.608	neutral	N	0.504141281	None	None	I
Y/P	0.9606	likely_pathogenic	0.9677	pathogenic	-0.548	Destabilizing	0.987	D	0.659	neutral	None	None	None	None	I
Y/Q	0.6144	likely_pathogenic	0.6245	pathogenic	-0.019	Destabilizing	0.987	D	0.571	neutral	None	None	None	None	I
Y/R	0.613	likely_pathogenic	0.6159	pathogenic	0.473	Stabilizing	0.987	D	0.614	neutral	None	None	None	None	I
Y/S	0.3167	likely_benign	0.3339	benign	-0.498	Destabilizing	0.967	D	0.462	neutral	N	0.496060515	None	None	I
Y/T	0.6475	likely_pathogenic	0.6499	pathogenic	-0.427	Destabilizing	0.975	D	0.563	neutral	None	None	None	None	I
Y/V	0.6062	likely_pathogenic	0.59	pathogenic	-0.548	Destabilizing	0.987	D	0.513	neutral	None	None	None	None	I
Y/W	0.6045	likely_pathogenic	0.6011	pathogenic	-0.54	Destabilizing	0.999	D	0.556	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.