TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20515	61768;61769;61770	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
N2AB	18874	56845;56846;56847	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
N2A	17947	54064;54065;54066	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
N2B	11450	34573;34574;34575	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
Novex-1	11575	34948;34949;34950	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
Novex-2	11642	35149;35150;35151	chr2:178590182;178590181;178590180	chr2:179454909;179454908;179454907
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: Ig-121
• Domain position: 37
• Structural Position: 55
• Q(SASA): 0.6824
• 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/Q	None	None	0.801	N	0.357	0.228	0.225215365344	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.2836	likely_benign	0.2757	benign	0.031	Stabilizing	0.525	D	0.375	neutral	None	None	None	None	N
K/C	0.5799	likely_pathogenic	0.5245	ambiguous	-0.342	Destabilizing	0.998	D	0.358	neutral	None	None	None	None	N
K/D	0.4446	ambiguous	0.4556	ambiguous	0.071	Stabilizing	0.842	D	0.388	neutral	None	None	None	None	N
K/E	0.154	likely_benign	0.1596	benign	0.086	Stabilizing	0.801	D	0.325	neutral	N	0.449075511	None	None	N
K/F	0.7167	likely_pathogenic	0.696	pathogenic	-0.181	Destabilizing	0.991	D	0.365	neutral	None	None	None	None	N
K/G	0.4171	ambiguous	0.4137	ambiguous	-0.161	Destabilizing	0.842	D	0.347	neutral	None	None	None	None	N
K/H	0.2404	likely_benign	0.2172	benign	-0.333	Destabilizing	0.974	D	0.351	neutral	None	None	None	None	N
K/I	0.2956	likely_benign	0.2868	benign	0.455	Stabilizing	0.934	D	0.391	neutral	N	0.482478795	None	None	N
K/L	0.3295	likely_benign	0.3257	benign	0.455	Stabilizing	0.842	D	0.385	neutral	None	None	None	None	N
K/M	0.2109	likely_benign	0.2096	benign	0.114	Stabilizing	0.991	D	0.351	neutral	None	None	None	None	N
K/N	0.2772	likely_benign	0.2801	benign	0.093	Stabilizing	0.801	D	0.317	neutral	N	0.494349227	None	None	N
K/P	0.884	likely_pathogenic	0.8921	pathogenic	0.341	Stabilizing	0.974	D	0.338	neutral	None	None	None	None	N
K/Q	0.1111	likely_benign	0.1065	benign	-0.027	Destabilizing	0.801	D	0.357	neutral	N	0.425737291	None	None	N
K/R	0.078	likely_benign	0.0742	benign	-0.048	Destabilizing	0.012	N	0.273	neutral	N	0.419390109	None	None	N
K/S	0.3312	likely_benign	0.3301	benign	-0.372	Destabilizing	0.172	N	0.289	neutral	None	None	None	None	N
K/T	0.1544	likely_benign	0.1547	benign	-0.208	Destabilizing	0.022	N	0.231	neutral	N	0.463199601	None	None	N
K/V	0.2656	likely_benign	0.2522	benign	0.341	Stabilizing	0.842	D	0.385	neutral	None	None	None	None	N
K/W	0.7636	likely_pathogenic	0.7215	pathogenic	-0.233	Destabilizing	0.998	D	0.392	neutral	None	None	None	None	N
K/Y	0.5833	likely_pathogenic	0.549	ambiguous	0.127	Stabilizing	0.991	D	0.371	neutral	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.