TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25603	77032;77033;77034	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
N2AB	23962	72109;72110;72111	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
N2A	23035	69328;69329;69330	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
N2B	16538	49837;49838;49839	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
Novex-1	16663	50212;50213;50214	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
Novex-2	16730	50413;50414;50415	chr2:178569325;178569324;178569323	chr2:179434052;179434051;179434050
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: Fn3-74
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2109
• 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/G	rs1446500939	-1.307	0.011	N	0.31	0.097	0.159798565429	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/G	rs1446500939	-1.307	0.011	N	0.31	0.097	0.159798565429	gnomAD-4.0.0	6.57341E-06	None	None	None	None	I	None	2.41208E-05	0	None	0	0	None	0	0	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	0.1294	likely_benign	0.1416	benign	-0.851	Destabilizing	0.702	D	0.565	neutral	None	None	None	None	I
S/C	0.2191	likely_benign	0.2521	benign	-0.746	Destabilizing	0.999	D	0.728	prob.delet.	N	0.514226793	None	None	I
S/D	0.7204	likely_pathogenic	0.7449	pathogenic	-0.86	Destabilizing	0.034	N	0.392	neutral	None	None	None	None	I
S/E	0.9101	likely_pathogenic	0.9247	pathogenic	-0.805	Destabilizing	0.851	D	0.571	neutral	None	None	None	None	I
S/F	0.6205	likely_pathogenic	0.6823	pathogenic	-0.817	Destabilizing	0.996	D	0.807	deleterious	None	None	None	None	I
S/G	0.0758	likely_benign	0.0865	benign	-1.14	Destabilizing	0.011	N	0.31	neutral	N	0.420469465	None	None	I
S/H	0.7726	likely_pathogenic	0.8028	pathogenic	-1.522	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
S/I	0.7063	likely_pathogenic	0.753	pathogenic	-0.167	Destabilizing	0.995	D	0.81	deleterious	N	0.502870488	None	None	I
S/K	0.9789	likely_pathogenic	0.9833	pathogenic	-0.74	Destabilizing	0.919	D	0.617	neutral	None	None	None	None	I
S/L	0.275	likely_benign	0.3041	benign	-0.167	Destabilizing	0.988	D	0.796	deleterious	None	None	None	None	I
S/M	0.4893	ambiguous	0.5315	ambiguous	-0.043	Destabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	I
S/N	0.4193	ambiguous	0.4364	ambiguous	-0.881	Destabilizing	0.896	D	0.587	neutral	N	0.485447342	None	None	I
S/P	0.9545	likely_pathogenic	0.9672	pathogenic	-0.361	Destabilizing	0.996	D	0.746	deleterious	None	None	None	None	I
S/Q	0.8848	likely_pathogenic	0.9029	pathogenic	-0.988	Destabilizing	0.988	D	0.628	neutral	None	None	None	None	I
S/R	0.971	likely_pathogenic	0.9785	pathogenic	-0.705	Destabilizing	0.984	D	0.738	prob.delet.	N	0.512959346	None	None	I
S/T	0.3003	likely_benign	0.3238	benign	-0.808	Destabilizing	0.946	D	0.579	neutral	N	0.494348112	None	None	I
S/V	0.6708	likely_pathogenic	0.717	pathogenic	-0.361	Destabilizing	0.988	D	0.788	deleterious	None	None	None	None	I
S/W	0.8346	likely_pathogenic	0.8657	pathogenic	-0.831	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
S/Y	0.5998	likely_pathogenic	0.645	pathogenic	-0.536	Destabilizing	0.996	D	0.819	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.