TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18253	54982;54983;54984	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
N2AB	16612	50059;50060;50061	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
N2A	15685	47278;47279;47280	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
N2B	9188	27787;27788;27789	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
Novex-1	9313	28162;28163;28164	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
Novex-2	9380	28363;28364;28365	chr2:178603930;178603929;178603928	chr2:179468657;179468656;179468655
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-20
• Domain position: 88
• Structural Position: 115
• Q(SASA): 0.1932
• 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
G/A	None	None	0.984	D	0.683	0.646	0.513167974481	gnomAD-4.0.0	1.59524E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86659E-06	0	0
G/R	None	None	0.513	D	0.659	0.7	0.692283160571	gnomAD-4.0.0	1.5949E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86587E-06	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
G/A	0.923	likely_pathogenic	0.8762	pathogenic	-0.545	Destabilizing	0.984	D	0.683	prob.neutral	D	0.559087762	None	None	I
G/C	0.9762	likely_pathogenic	0.959	pathogenic	-0.982	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/D	0.975	likely_pathogenic	0.9601	pathogenic	-0.765	Destabilizing	0.997	D	0.897	deleterious	None	None	None	None	I
G/E	0.9881	likely_pathogenic	0.9797	pathogenic	-0.899	Destabilizing	0.996	D	0.899	deleterious	D	0.559087762	None	None	I
G/F	0.9976	likely_pathogenic	0.9952	pathogenic	-1.065	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	I
G/H	0.9935	likely_pathogenic	0.9888	pathogenic	-0.818	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
G/I	0.9972	likely_pathogenic	0.9943	pathogenic	-0.519	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
G/K	0.9901	likely_pathogenic	0.9854	pathogenic	-1.134	Destabilizing	0.993	D	0.892	deleterious	None	None	None	None	I
G/L	0.9949	likely_pathogenic	0.9909	pathogenic	-0.519	Destabilizing	0.997	D	0.887	deleterious	None	None	None	None	I
G/M	0.9966	likely_pathogenic	0.994	pathogenic	-0.534	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
G/N	0.9776	likely_pathogenic	0.9681	pathogenic	-0.794	Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	I
G/P	0.9994	likely_pathogenic	0.9989	pathogenic	-0.491	Destabilizing	0.999	D	0.905	deleterious	None	None	None	None	I
G/Q	0.9855	likely_pathogenic	0.9769	pathogenic	-1.058	Destabilizing	0.997	D	0.905	deleterious	None	None	None	None	I
G/R	0.9778	likely_pathogenic	0.9631	pathogenic	-0.66	Destabilizing	0.513	D	0.659	neutral	D	0.559341252	None	None	I
G/S	0.8477	likely_pathogenic	0.7832	pathogenic	-0.98	Destabilizing	0.997	D	0.86	deleterious	None	None	None	None	I
G/T	0.9777	likely_pathogenic	0.9649	pathogenic	-1.041	Destabilizing	0.997	D	0.899	deleterious	None	None	None	None	I
G/V	0.9932	likely_pathogenic	0.9857	pathogenic	-0.491	Destabilizing	0.998	D	0.877	deleterious	D	0.533096695	None	None	I
G/W	0.9949	likely_pathogenic	0.9895	pathogenic	-1.254	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
G/Y	0.9949	likely_pathogenic	0.9904	pathogenic	-0.912	Destabilizing	1.0	D	0.899	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.