TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28915	86968;86969;86970	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
N2AB	27274	82045;82046;82047	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
N2A	26347	79264;79265;79266	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
N2B	19850	59773;59774;59775	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
Novex-1	19975	60148;60149;60150	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
Novex-2	20042	60349;60350;60351	chr2:178559389;178559388;178559387	chr2:179424116;179424115;179424114
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: Fn3-98
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.0913
• 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/C	rs764006835	-1.253	1.0	D	0.845	0.823	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
Y/C	rs764006835	-1.253	1.0	D	0.845	0.823	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Y/C	rs764006835	-1.253	1.0	D	0.845	0.823	None	gnomAD-4.0.0	6.57065E-06	None	None	None	None	N	None	2.4122E-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
Y/A	0.9766	likely_pathogenic	0.981	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/C	0.6155	likely_pathogenic	0.6634	pathogenic	-1.607	Destabilizing	1.0	D	0.845	deleterious	D	0.663184979	None	None	N
Y/D	0.9896	likely_pathogenic	0.9909	pathogenic	-3.515	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.663184979	None	None	N
Y/E	0.9969	likely_pathogenic	0.9974	pathogenic	-3.298	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/F	0.152	likely_benign	0.1716	benign	-1.066	Destabilizing	0.999	D	0.771	deleterious	D	0.607970871	None	None	N
Y/G	0.9662	likely_pathogenic	0.9707	pathogenic	-3.387	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/H	0.843	likely_pathogenic	0.8699	pathogenic	-2.081	Highly Destabilizing	1.0	D	0.827	deleterious	D	0.663184979	None	None	N
Y/I	0.9223	likely_pathogenic	0.9405	pathogenic	-1.576	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
Y/K	0.9969	likely_pathogenic	0.9977	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
Y/L	0.8817	likely_pathogenic	0.9067	pathogenic	-1.576	Destabilizing	0.997	D	0.812	deleterious	None	None	None	None	N
Y/M	0.9656	likely_pathogenic	0.9733	pathogenic	-1.255	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/N	0.8965	likely_pathogenic	0.9168	pathogenic	-3.162	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.662983175	None	None	N
Y/P	0.9963	likely_pathogenic	0.9968	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9882	likely_pathogenic	0.9909	pathogenic	-2.869	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
Y/R	0.9833	likely_pathogenic	0.9866	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/S	0.8818	likely_pathogenic	0.8975	pathogenic	-3.444	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.663184979	None	None	N
Y/T	0.967	likely_pathogenic	0.973	pathogenic	-3.106	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/V	0.8689	likely_pathogenic	0.8926	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/W	0.7079	likely_pathogenic	0.7024	pathogenic	-0.397	Destabilizing	1.0	D	0.802	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.