TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24929	75010;75011;75012	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
N2AB	23288	70087;70088;70089	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
N2A	22361	67306;67307;67308	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
N2B	15864	47815;47816;47817	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
Novex-1	15989	48190;48191;48192	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
Novex-2	16056	48391;48392;48393	chr2:178571347;178571346;178571345	chr2:179436074;179436073;179436072
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-69
• Domain position: 22
• Structural Position: 24
• Q(SASA): 0.1041
• 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
W/R	None	None	0.994	D	0.905	0.845	0.899303468351	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85972E-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
W/A	0.9978	likely_pathogenic	0.9973	pathogenic	-4.004	Highly Destabilizing	0.845	D	0.866	deleterious	None	None	None	None	N
W/C	0.9981	likely_pathogenic	0.9978	pathogenic	-2.097	Highly Destabilizing	0.056	N	0.742	deleterious	D	0.68065092	None	None	N
W/D	0.9997	likely_pathogenic	0.9997	pathogenic	-4.073	Highly Destabilizing	0.996	D	0.893	deleterious	None	None	None	None	N
W/E	0.9997	likely_pathogenic	0.9996	pathogenic	-3.967	Highly Destabilizing	0.996	D	0.897	deleterious	None	None	None	None	N
W/F	0.8674	likely_pathogenic	0.8719	pathogenic	-2.694	Highly Destabilizing	0.987	D	0.792	deleterious	None	None	None	None	N
W/G	0.9852	likely_pathogenic	0.9819	pathogenic	-4.213	Highly Destabilizing	0.983	D	0.847	deleterious	D	0.68065092	None	None	N
W/H	0.9983	likely_pathogenic	0.998	pathogenic	-3.171	Highly Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
W/I	0.9963	likely_pathogenic	0.9959	pathogenic	-3.154	Highly Destabilizing	0.975	D	0.896	deleterious	None	None	None	None	N
W/K	0.9998	likely_pathogenic	0.9998	pathogenic	-3.055	Highly Destabilizing	0.987	D	0.893	deleterious	None	None	None	None	N
W/L	0.9902	likely_pathogenic	0.9888	pathogenic	-3.154	Highly Destabilizing	0.805	D	0.839	deleterious	D	0.679641899	None	None	N
W/M	0.9972	likely_pathogenic	0.9968	pathogenic	-2.446	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
W/N	0.9996	likely_pathogenic	0.9996	pathogenic	-3.662	Highly Destabilizing	0.996	D	0.901	deleterious	None	None	None	None	N
W/P	0.9997	likely_pathogenic	0.9997	pathogenic	-3.471	Highly Destabilizing	0.996	D	0.902	deleterious	None	None	None	None	N
W/Q	0.9998	likely_pathogenic	0.9997	pathogenic	-3.566	Highly Destabilizing	0.996	D	0.884	deleterious	None	None	None	None	N
W/R	0.9996	likely_pathogenic	0.9995	pathogenic	-2.599	Highly Destabilizing	0.994	D	0.905	deleterious	D	0.68065092	None	None	N
W/S	0.9968	likely_pathogenic	0.9961	pathogenic	-3.8	Highly Destabilizing	0.967	D	0.889	deleterious	D	0.68065092	None	None	N
W/T	0.9987	likely_pathogenic	0.9984	pathogenic	-3.626	Highly Destabilizing	0.975	D	0.842	deleterious	None	None	None	None	N
W/V	0.996	likely_pathogenic	0.9957	pathogenic	-3.471	Highly Destabilizing	0.975	D	0.886	deleterious	None	None	None	None	N
W/Y	0.9639	likely_pathogenic	0.9635	pathogenic	-2.579	Highly Destabilizing	0.996	D	0.794	deleterious	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.