TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15793	47602;47603;47604	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
N2AB	14152	42679;42680;42681	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
N2A	13225	39898;39899;39900	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
N2B	6728	20407;20408;20409	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
Novex-1	6853	20782;20783;20784	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
Novex-2	6920	20983;20984;20985	chr2:178617974;178617973;178617972	chr2:179482701;179482700;179482699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-2
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.0719
• 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
Y/D	None	None	1.0	D	0.887	0.901	0.935313694348	gnomAD-4.0.0	1.59348E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02975E-05
Y/H	None	None	1.0	D	0.792	0.887	0.798173959035	gnomAD-4.0.0	1.59348E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8627E-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
Y/A	0.9941	likely_pathogenic	0.9937	pathogenic	-3.895	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
Y/C	0.9349	likely_pathogenic	0.9198	pathogenic	-2.244	Highly Destabilizing	1.0	D	0.846	deleterious	D	0.835178775	None	None	N
Y/D	0.9952	likely_pathogenic	0.9948	pathogenic	-3.942	Highly Destabilizing	1.0	D	0.887	deleterious	D	0.83480847	None	None	N
Y/E	0.9987	likely_pathogenic	0.9985	pathogenic	-3.734	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/F	0.3186	likely_benign	0.2921	benign	-1.616	Destabilizing	0.999	D	0.663	neutral	D	0.644460483	None	None	N
Y/G	0.9883	likely_pathogenic	0.9873	pathogenic	-4.271	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/H	0.9648	likely_pathogenic	0.9594	pathogenic	-2.885	Highly Destabilizing	1.0	D	0.792	deleterious	D	0.782641448	None	None	N
Y/I	0.9718	likely_pathogenic	0.97	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
Y/K	0.9978	likely_pathogenic	0.9976	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/L	0.9336	likely_pathogenic	0.9278	pathogenic	-2.595	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
Y/M	0.9838	likely_pathogenic	0.9817	pathogenic	-2.336	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
Y/N	0.9797	likely_pathogenic	0.9769	pathogenic	-3.457	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.835178775	None	None	N
Y/P	0.9994	likely_pathogenic	0.9993	pathogenic	-3.05	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
Y/Q	0.998	likely_pathogenic	0.9977	pathogenic	-3.214	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Y/R	0.9894	likely_pathogenic	0.988	pathogenic	-2.433	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
Y/S	0.9871	likely_pathogenic	0.9856	pathogenic	-3.773	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.835178775	None	None	N
Y/T	0.9922	likely_pathogenic	0.9913	pathogenic	-3.456	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/V	0.9447	likely_pathogenic	0.9401	pathogenic	-3.05	Highly Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
Y/W	0.8793	likely_pathogenic	0.8586	pathogenic	-0.775	Destabilizing	1.0	D	0.78	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.