TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27365	82318;82319;82320	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
N2AB	25724	77395;77396;77397	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
N2A	24797	74614;74615;74616	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
N2B	18300	55123;55124;55125	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
Novex-1	18425	55498;55499;55500	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
Novex-2	18492	55699;55700;55701	chr2:178564039;178564038;178564037	chr2:179428766;179428765;179428764
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: Ig-140
• Domain position: 88
• Structural Position: 175
• Q(SASA): 0.5607
• Predicted PPI site: I

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/R	None	None	0.999	N	0.591	0.319	0.486567385682	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.586	likely_pathogenic	0.6816	pathogenic	-0.387	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	I
K/C	0.7525	likely_pathogenic	0.7985	pathogenic	-0.59	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/D	0.798	likely_pathogenic	0.8598	pathogenic	0.096	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/E	0.3318	likely_benign	0.4301	ambiguous	0.217	Stabilizing	0.999	D	0.643	neutral	N	0.486617836	None	None	I
K/F	0.866	likely_pathogenic	0.9126	pathogenic	-0.05	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
K/G	0.8003	likely_pathogenic	0.8722	pathogenic	-0.742	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/H	0.3407	ambiguous	0.3898	ambiguous	-0.909	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
K/I	0.4343	ambiguous	0.5027	ambiguous	0.526	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
K/L	0.453	ambiguous	0.5264	ambiguous	0.526	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/M	0.2854	likely_benign	0.3407	ambiguous	0.144	Stabilizing	1.0	D	0.629	neutral	N	0.516411246	None	None	I
K/N	0.5775	likely_pathogenic	0.6788	pathogenic	-0.435	Destabilizing	1.0	D	0.691	prob.neutral	N	0.485265164	None	None	I
K/P	0.9833	likely_pathogenic	0.9907	pathogenic	0.252	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/Q	0.1821	likely_benign	0.2214	benign	-0.418	Destabilizing	1.0	D	0.687	prob.neutral	N	0.488668524	None	None	I
K/R	0.0895	likely_benign	0.0983	benign	-0.464	Destabilizing	0.999	D	0.591	neutral	N	0.49586938	None	None	I
K/S	0.6107	likely_pathogenic	0.7075	pathogenic	-1.052	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
K/T	0.2377	likely_benign	0.2969	benign	-0.724	Destabilizing	1.0	D	0.708	prob.delet.	N	0.517319301	None	None	I
K/V	0.4058	ambiguous	0.4658	ambiguous	0.252	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
K/W	0.8232	likely_pathogenic	0.8823	pathogenic	0.017	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
K/Y	0.7355	likely_pathogenic	0.8019	pathogenic	0.315	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I

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.