TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28948	87067;87068;87069	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
N2AB	27307	82144;82145;82146	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
N2A	26380	79363;79364;79365	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
N2B	19883	59872;59873;59874	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
Novex-1	20008	60247;60248;60249	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
Novex-2	20075	60448;60449;60450	chr2:178558617;178558616;178558615	chr2:179423344;179423343;179423342
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-99
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5647
• 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
K/N	rs768882533	-0.234	0.986	N	0.663	0.21	0.193865811164	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.37E-05	None	0	0	0
K/N	rs768882533	-0.234	0.986	N	0.663	0.21	0.193865811164	gnomAD-4.0.0	1.59592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4486E-05	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
K/A	0.6127	likely_pathogenic	0.5133	ambiguous	-0.036	Destabilizing	0.963	D	0.585	neutral	None	None	None	None	I
K/C	0.7992	likely_pathogenic	0.7576	pathogenic	-0.328	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
K/D	0.7107	likely_pathogenic	0.6379	pathogenic	0.092	Stabilizing	0.995	D	0.727	prob.delet.	None	None	None	None	I
K/E	0.4394	ambiguous	0.3603	ambiguous	0.112	Stabilizing	0.854	D	0.535	neutral	N	0.480211202	None	None	I
K/F	0.8744	likely_pathogenic	0.832	pathogenic	-0.174	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
K/G	0.6386	likely_pathogenic	0.5571	ambiguous	-0.25	Destabilizing	0.989	D	0.629	neutral	None	None	None	None	I
K/H	0.3848	ambiguous	0.3454	ambiguous	-0.435	Destabilizing	0.997	D	0.695	prob.neutral	None	None	None	None	I
K/I	0.6098	likely_pathogenic	0.5125	ambiguous	0.454	Stabilizing	0.802	D	0.749	deleterious	N	0.471355558	None	None	I
K/L	0.564	likely_pathogenic	0.497	ambiguous	0.454	Stabilizing	0.726	D	0.629	neutral	None	None	None	None	I
K/M	0.3961	ambiguous	0.3217	benign	0.148	Stabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	I
K/N	0.508	ambiguous	0.4445	ambiguous	0.098	Stabilizing	0.986	D	0.663	neutral	N	0.410364328	None	None	I
K/P	0.9168	likely_pathogenic	0.8902	pathogenic	0.319	Stabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	I
K/Q	0.2127	likely_benign	0.1839	benign	-0.043	Destabilizing	0.892	D	0.657	neutral	N	0.474554666	None	None	I
K/R	0.09	likely_benign	0.0875	benign	-0.069	Destabilizing	0.025	N	0.269	neutral	N	0.436748427	None	None	I
K/S	0.6383	likely_pathogenic	0.5469	ambiguous	-0.406	Destabilizing	0.963	D	0.614	neutral	None	None	None	None	I
K/T	0.4032	ambiguous	0.3126	benign	-0.23	Destabilizing	0.953	D	0.682	prob.neutral	N	0.473362588	None	None	I
K/V	0.5676	likely_pathogenic	0.4658	ambiguous	0.319	Stabilizing	0.876	D	0.725	prob.delet.	None	None	None	None	I
K/W	0.8538	likely_pathogenic	0.8213	pathogenic	-0.183	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
K/Y	0.6701	likely_pathogenic	0.6139	pathogenic	0.161	Stabilizing	0.963	D	0.744	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.