TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28938	87037;87038;87039	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
N2AB	27297	82114;82115;82116	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
N2A	26370	79333;79334;79335	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
N2B	19873	59842;59843;59844	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
Novex-1	19998	60217;60218;60219	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
Novex-2	20065	60418;60419;60420	chr2:178559320;178559319;178559318	chr2:179424047;179424046;179424045
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: Fn3-98
• Domain position: 94
• Structural Position: 129
• Q(SASA): 0.7491
• 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/N	rs770082146	0.043	0.999	N	0.72	0.25	0.197625483188	gnomAD-2.1.1	4.27E-06	None	None	None	None	N	None	0	3.18E-05	None	0	0	None	0	None	0	0	0
K/N	rs770082146	0.043	0.999	N	0.72	0.25	0.197625483188	gnomAD-4.0.0	3.31181E-06	None	None	None	None	N	None	0	4.98753E-05	None	0	0	None	0	0	0	0	0
K/R	None	None	0.185	N	0.419	0.079	0.197625483188	gnomAD-4.0.0	1.2004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31258E-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	0.7026	likely_pathogenic	0.7564	pathogenic	-0.257	Destabilizing	0.998	D	0.657	prob.neutral	None	None	None	None	N
K/C	0.7865	likely_pathogenic	0.8329	pathogenic	-0.52	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
K/D	0.9519	likely_pathogenic	0.965	pathogenic	0.339	Stabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/E	0.6116	likely_pathogenic	0.6602	pathogenic	0.403	Stabilizing	0.981	D	0.661	prob.neutral	N	0.470729539	None	None	N
K/F	0.8948	likely_pathogenic	0.9163	pathogenic	-0.212	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/G	0.8762	likely_pathogenic	0.9016	pathogenic	-0.533	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
K/H	0.5264	ambiguous	0.5865	pathogenic	-0.725	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/I	0.5066	ambiguous	0.5382	ambiguous	0.416	Stabilizing	0.991	D	0.779	deleterious	N	0.463310026	None	None	N
K/L	0.4831	ambiguous	0.521	ambiguous	0.416	Stabilizing	0.979	D	0.563	neutral	None	None	None	None	N
K/M	0.3635	ambiguous	0.3963	ambiguous	0.118	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/N	0.8295	likely_pathogenic	0.8716	pathogenic	-0.115	Destabilizing	0.999	D	0.72	deleterious	N	0.497481075	None	None	N
K/P	0.8825	likely_pathogenic	0.8951	pathogenic	0.222	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Q	0.267	likely_benign	0.3002	benign	-0.207	Destabilizing	0.986	D	0.745	deleterious	N	0.470983029	None	None	N
K/R	0.0944	likely_benign	0.0978	benign	-0.203	Destabilizing	0.185	N	0.419	neutral	N	0.489923977	None	None	N
K/S	0.825	likely_pathogenic	0.8653	pathogenic	-0.75	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
K/T	0.4111	ambiguous	0.462	ambiguous	-0.502	Destabilizing	0.997	D	0.673	prob.neutral	N	0.457624265	None	None	N
K/V	0.4785	ambiguous	0.5115	ambiguous	0.222	Stabilizing	0.984	D	0.726	deleterious	None	None	None	None	N
K/W	0.8586	likely_pathogenic	0.8902	pathogenic	-0.138	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/Y	0.8061	likely_pathogenic	0.848	pathogenic	0.185	Stabilizing	0.996	D	0.773	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.