TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23254	69985;69986;69987	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
N2AB	21613	65062;65063;65064	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
N2A	20686	62281;62282;62283	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
N2B	14189	42790;42791;42792	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
Novex-1	14314	43165;43166;43167	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
Novex-2	14381	43366;43367;43368	chr2:178576372;178576371;178576370	chr2:179441099;179441098;179441097
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-57
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5686
• 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
K/E	rs892446768	None	0.981	N	0.587	0.344	0.311691414656	gnomAD-4.0.0	1.74224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.02977E-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
K/A	0.4468	ambiguous	0.3294	benign	-0.144	Destabilizing	0.845	D	0.571	neutral	None	None	None	None	N
K/C	0.8027	likely_pathogenic	0.6932	pathogenic	-0.243	Destabilizing	0.073	N	0.577	neutral	None	None	None	None	N
K/D	0.8042	likely_pathogenic	0.6918	pathogenic	0.022	Stabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	N
K/E	0.3263	likely_benign	0.2408	benign	0.043	Stabilizing	0.981	D	0.587	neutral	N	0.511147398	None	None	N
K/F	0.9169	likely_pathogenic	0.8298	pathogenic	-0.247	Destabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
K/G	0.5252	ambiguous	0.3981	ambiguous	-0.392	Destabilizing	0.987	D	0.622	neutral	None	None	None	None	N
K/H	0.5173	ambiguous	0.391	ambiguous	-0.761	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/I	0.6184	likely_pathogenic	0.4811	ambiguous	0.442	Stabilizing	0.975	D	0.737	prob.delet.	None	None	None	None	N
K/L	0.5438	ambiguous	0.3961	ambiguous	0.442	Stabilizing	0.845	D	0.607	neutral	None	None	None	None	N
K/M	0.4178	ambiguous	0.2878	benign	0.37	Stabilizing	0.999	D	0.649	neutral	N	0.503729407	None	None	N
K/N	0.7003	likely_pathogenic	0.5622	ambiguous	0.078	Stabilizing	0.994	D	0.666	neutral	D	0.5226739	None	None	N
K/P	0.7259	likely_pathogenic	0.6239	pathogenic	0.276	Stabilizing	0.996	D	0.668	neutral	None	None	None	None	N
K/Q	0.1905	likely_benign	0.1485	benign	-0.132	Destabilizing	0.994	D	0.675	neutral	N	0.466506939	None	None	N
K/R	0.082	likely_benign	0.0774	benign	-0.198	Destabilizing	0.981	D	0.564	neutral	N	0.47030364	None	None	N
K/S	0.5683	likely_pathogenic	0.4306	ambiguous	-0.478	Destabilizing	0.916	D	0.591	neutral	None	None	None	None	N
K/T	0.3662	ambiguous	0.2625	benign	-0.293	Destabilizing	0.967	D	0.636	neutral	N	0.466454033	None	None	N
K/V	0.5266	ambiguous	0.3928	ambiguous	0.276	Stabilizing	0.975	D	0.626	neutral	None	None	None	None	N
K/W	0.8802	likely_pathogenic	0.7923	pathogenic	-0.186	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/Y	0.8106	likely_pathogenic	0.6863	pathogenic	0.148	Stabilizing	0.996	D	0.723	prob.delet.	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.