TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25474	76645;76646;76647	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
N2AB	23833	71722;71723;71724	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
N2A	22906	68941;68942;68943	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
N2B	16409	49450;49451;49452	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
Novex-1	16534	49825;49826;49827	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
Novex-2	16601	50026;50027;50028	chr2:178569712;178569711;178569710	chr2:179434439;179434438;179434437
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: Fn3-73
• Domain position: 70
• Structural Position: 100
• Q(SASA): 0.7052
• 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/M	rs1707440249	None	0.999	N	0.7	0.441	0.322510055762	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
K/M	rs1707440249	None	0.999	N	0.7	0.441	0.322510055762	gnomAD-4.0.0	2.56444E-06	None	None	None	None	N	None	3.38352E-05	0	None	0	0	None	0	0	0	0	0
K/N	rs786205301	0.078	0.967	N	0.697	0.261	0.17258766438	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs786205301	0.078	0.967	N	0.697	0.261	0.17258766438	gnomAD-4.0.0	1.02677E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34945E-05	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	0.3663	ambiguous	0.3824	ambiguous	-0.153	Destabilizing	0.845	D	0.611	neutral	None	None	None	None	N
K/C	0.6039	likely_pathogenic	0.6446	pathogenic	-0.1	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
K/D	0.3522	ambiguous	0.3768	ambiguous	-0.057	Destabilizing	0.975	D	0.664	neutral	None	None	None	None	N
K/E	0.198	likely_benign	0.21	benign	0.008	Stabilizing	0.944	D	0.632	neutral	N	0.459009211	None	None	N
K/F	0.7445	likely_pathogenic	0.7668	pathogenic	0.027	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
K/G	0.2074	likely_benign	0.2208	benign	-0.446	Destabilizing	0.033	N	0.485	neutral	None	None	None	None	N
K/H	0.247	likely_benign	0.2654	benign	-0.713	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
K/I	0.5617	ambiguous	0.5782	pathogenic	0.578	Stabilizing	0.996	D	0.767	deleterious	None	None	None	None	N
K/L	0.4134	ambiguous	0.4126	ambiguous	0.578	Stabilizing	0.987	D	0.657	neutral	None	None	None	None	N
K/M	0.2579	likely_benign	0.2565	benign	0.239	Stabilizing	0.999	D	0.7	prob.neutral	N	0.491198987	None	None	N
K/N	0.1813	likely_benign	0.1946	benign	0.061	Stabilizing	0.967	D	0.697	prob.neutral	N	0.37067815	None	None	N
K/P	0.7528	likely_pathogenic	0.7457	pathogenic	0.364	Stabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.1366	likely_benign	0.1388	benign	-0.007	Destabilizing	0.994	D	0.713	prob.delet.	N	0.474344022	None	None	N
K/R	0.0962	likely_benign	0.0968	benign	-0.277	Destabilizing	0.944	D	0.607	neutral	N	0.476768252	None	None	N
K/S	0.2986	likely_benign	0.3169	benign	-0.393	Destabilizing	0.916	D	0.656	neutral	None	None	None	None	N
K/T	0.2078	likely_benign	0.2102	benign	-0.16	Destabilizing	0.983	D	0.664	neutral	N	0.520308386	None	None	N
K/V	0.5125	ambiguous	0.5189	ambiguous	0.364	Stabilizing	0.987	D	0.725	prob.delet.	None	None	None	None	N
K/W	0.766	likely_pathogenic	0.7692	pathogenic	0.028	Stabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
K/Y	0.5169	ambiguous	0.5407	ambiguous	0.305	Stabilizing	0.996	D	0.758	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.