TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26523	79792;79793;79794	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
N2AB	24882	74869;74870;74871	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
N2A	23955	72088;72089;72090	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
N2B	17458	52597;52598;52599	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
Novex-1	17583	52972;52973;52974	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
Novex-2	17650	53173;53174;53175	chr2:178566565;178566564;178566563	chr2:179431292;179431291;179431290
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-81
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1697
• 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
V/A	None	None	0.001	N	0.319	0.206	0.606876268242	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
V/A	0.1473	likely_benign	0.1468	benign	-2.169	Highly Destabilizing	0.001	N	0.319	neutral	N	0.511360828	None	None	N
V/C	0.5361	ambiguous	0.5789	pathogenic	-1.883	Destabilizing	0.935	D	0.683	prob.neutral	None	None	None	None	N
V/D	0.5861	likely_pathogenic	0.6361	pathogenic	-2.788	Highly Destabilizing	0.555	D	0.681	prob.neutral	None	None	None	None	N
V/E	0.3643	ambiguous	0.415	ambiguous	-2.583	Highly Destabilizing	0.484	N	0.649	neutral	N	0.514782349	None	None	N
V/F	0.1594	likely_benign	0.1745	benign	-1.266	Destabilizing	0.235	N	0.695	prob.neutral	None	None	None	None	N
V/G	0.3261	likely_benign	0.3362	benign	-2.685	Highly Destabilizing	0.117	N	0.629	neutral	N	0.491283465	None	None	N
V/H	0.4497	ambiguous	0.5223	ambiguous	-2.364	Highly Destabilizing	0.935	D	0.69	prob.neutral	None	None	None	None	N
V/I	0.0669	likely_benign	0.0673	benign	-0.732	Destabilizing	None	N	0.317	neutral	N	0.426224789	None	None	N
V/K	0.3147	likely_benign	0.3896	ambiguous	-1.807	Destabilizing	0.149	N	0.652	neutral	None	None	None	None	N
V/L	0.1185	likely_benign	0.1268	benign	-0.732	Destabilizing	None	N	0.297	neutral	N	0.475093384	None	None	N
V/M	0.092	likely_benign	0.0937	benign	-0.936	Destabilizing	0.005	N	0.515	neutral	None	None	None	None	N
V/N	0.318	likely_benign	0.3586	ambiguous	-2.116	Highly Destabilizing	0.555	D	0.679	prob.neutral	None	None	None	None	N
V/P	0.9628	likely_pathogenic	0.9652	pathogenic	-1.185	Destabilizing	0.555	D	0.653	neutral	None	None	None	None	N
V/Q	0.2818	likely_benign	0.3332	benign	-1.986	Destabilizing	0.555	D	0.649	neutral	None	None	None	None	N
V/R	0.2617	likely_benign	0.327	benign	-1.603	Destabilizing	0.38	N	0.681	prob.neutral	None	None	None	None	N
V/S	0.2034	likely_benign	0.215	benign	-2.727	Highly Destabilizing	0.081	N	0.62	neutral	None	None	None	None	N
V/T	0.1394	likely_benign	0.1417	benign	-2.384	Highly Destabilizing	0.149	N	0.687	prob.neutral	None	None	None	None	N
V/W	0.6928	likely_pathogenic	0.7346	pathogenic	-1.742	Destabilizing	0.935	D	0.691	prob.neutral	None	None	None	None	N
V/Y	0.4148	ambiguous	0.4688	ambiguous	-1.394	Destabilizing	0.555	D	0.687	prob.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.