TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7576	22951;22952;22953	chr2:178721937;178721936;178721935	chr2:179586664;179586663;179586662
N2AB	7259	22000;22001;22002	chr2:178721937;178721936;178721935	chr2:179586664;179586663;179586662
N2A	6332	19219;19220;19221	chr2:178721937;178721936;178721935	chr2:179586664;179586663;179586662
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-60
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.7036
• 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/I	None	None	0.43	N	0.683	0.329	0.422762650823	gnomAD-4.0.0	6.84323E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15974E-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	0.6612	likely_pathogenic	0.6695	pathogenic	-0.117	Destabilizing	0.667	D	0.591	neutral	None	None	None	None	N
K/C	0.8888	likely_pathogenic	0.8953	pathogenic	-0.211	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
K/D	0.7744	likely_pathogenic	0.7511	pathogenic	0.315	Stabilizing	0.971	D	0.59	neutral	None	None	None	None	N
K/E	0.524	ambiguous	0.519	ambiguous	0.329	Stabilizing	0.687	D	0.567	neutral	N	0.454053603	None	None	N
K/F	0.9239	likely_pathogenic	0.9333	pathogenic	-0.313	Destabilizing	0.988	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.6912	likely_pathogenic	0.694	pathogenic	-0.336	Destabilizing	0.906	D	0.597	neutral	None	None	None	None	N
K/H	0.3558	ambiguous	0.3585	ambiguous	-0.667	Destabilizing	0.991	D	0.599	neutral	None	None	None	None	N
K/I	0.804	likely_pathogenic	0.8114	pathogenic	0.382	Stabilizing	0.43	N	0.683	prob.neutral	N	0.479280552	None	None	N
K/L	0.6665	likely_pathogenic	0.6895	pathogenic	0.382	Stabilizing	0.222	N	0.606	neutral	None	None	None	None	N
K/M	0.5296	ambiguous	0.5361	ambiguous	0.326	Stabilizing	0.99	D	0.601	neutral	None	None	None	None	N
K/N	0.5794	likely_pathogenic	0.5478	ambiguous	0.285	Stabilizing	0.88	D	0.552	neutral	N	0.399485612	None	None	N
K/P	0.9399	likely_pathogenic	0.9443	pathogenic	0.245	Stabilizing	0.986	D	0.607	neutral	None	None	None	None	N
K/Q	0.2333	likely_benign	0.2407	benign	0.066	Stabilizing	0.756	D	0.577	neutral	N	0.468831054	None	None	N
K/R	0.083	likely_benign	0.0885	benign	0.014	Stabilizing	0.01	N	0.323	neutral	N	0.428619228	None	None	N
K/S	0.6631	likely_pathogenic	0.6732	pathogenic	-0.33	Destabilizing	0.274	N	0.316	neutral	None	None	None	None	N
K/T	0.4497	ambiguous	0.4729	ambiguous	-0.156	Destabilizing	0.029	N	0.327	neutral	N	0.474660949	None	None	N
K/V	0.7415	likely_pathogenic	0.7511	pathogenic	0.245	Stabilizing	0.568	D	0.58	neutral	None	None	None	None	N
K/W	0.871	likely_pathogenic	0.8802	pathogenic	-0.252	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
K/Y	0.7944	likely_pathogenic	0.7936	pathogenic	0.103	Stabilizing	0.907	D	0.672	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.