TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20953	63082;63083;63084	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
N2AB	19312	58159;58160;58161	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
N2A	18385	55378;55379;55380	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
N2B	11888	35887;35888;35889	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
Novex-1	12013	36262;36263;36264	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
Novex-2	12080	36463;36464;36465	chr2:178588868;178588867;178588866	chr2:179453595;179453594;179453593
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: Fn3-39
• Domain position: 90
• Structural Position: 124
• Q(SASA): 0.9153
• 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	rs765002114	0.012	0.961	N	0.608	0.084	0.178374595973	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	8.32E-05	0	None	0	0	None	0	None	0	3.91E-05	0
K/N	rs765002114	0.012	0.961	N	0.608	0.084	0.178374595973	gnomAD-3.1.2	3.95E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	8.83E-05	0	0
K/N	rs765002114	0.012	0.961	N	0.608	0.084	0.178374595973	gnomAD-4.0.0	1.79765E-05	None	None	None	None	N	None	2.67037E-05	0	None	0	0	None	0	1.64528E-04	2.11935E-05	0	1.60159E-05

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	0.2055	likely_benign	0.1734	benign	-0.044	Destabilizing	0.904	D	0.523	neutral	None	None	None	None	N
K/C	0.5515	ambiguous	0.4749	ambiguous	-0.572	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
K/D	0.3672	ambiguous	0.2891	benign	-0.324	Destabilizing	0.971	D	0.59	neutral	None	None	None	None	N
K/E	0.137	likely_benign	0.105	benign	-0.338	Destabilizing	0.877	D	0.595	neutral	N	0.395184232	None	None	N
K/F	0.608	likely_pathogenic	0.5223	ambiguous	-0.422	Destabilizing	0.985	D	0.773	deleterious	None	None	None	None	N
K/G	0.308	likely_benign	0.2647	benign	-0.152	Destabilizing	0.904	D	0.505	neutral	None	None	None	None	N
K/H	0.2682	likely_benign	0.2432	benign	-0.216	Destabilizing	0.064	N	0.509	neutral	None	None	None	None	N
K/I	0.2633	likely_benign	0.1967	benign	0.159	Stabilizing	0.981	D	0.777	deleterious	N	0.519438807	None	None	N
K/L	0.235	likely_benign	0.1833	benign	0.159	Stabilizing	0.971	D	0.493	neutral	None	None	None	None	N
K/M	0.2057	likely_benign	0.157	benign	-0.216	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
K/N	0.3044	likely_benign	0.2359	benign	-0.129	Destabilizing	0.961	D	0.608	neutral	N	0.48165121	None	None	N
K/P	0.3104	likely_benign	0.2657	benign	0.113	Stabilizing	0.995	D	0.659	prob.neutral	None	None	None	None	N
K/Q	0.116	likely_benign	0.105	benign	-0.246	Destabilizing	0.961	D	0.661	prob.neutral	N	0.479669697	None	None	N
K/R	0.087	likely_benign	0.0861	benign	-0.181	Destabilizing	0.022	N	0.311	neutral	N	0.501026405	None	None	N
K/S	0.27	likely_benign	0.2174	benign	-0.475	Destabilizing	0.904	D	0.581	neutral	None	None	None	None	N
K/T	0.1416	likely_benign	0.1145	benign	-0.378	Destabilizing	0.981	D	0.571	neutral	N	0.462892091	None	None	N
K/V	0.2177	likely_benign	0.1696	benign	0.113	Stabilizing	0.985	D	0.713	prob.delet.	None	None	None	None	N
K/W	0.6739	likely_pathogenic	0.6211	pathogenic	-0.543	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
K/Y	0.4983	ambiguous	0.4239	ambiguous	-0.193	Destabilizing	0.971	D	0.769	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.