TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29267	88024;88025;88026	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
N2AB	27626	83101;83102;83103	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
N2A	26699	80320;80321;80322	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
N2B	20202	60829;60830;60831	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
Novex-1	20327	61204;61205;61206	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
Novex-2	20394	61405;61406;61407	chr2:178557463;178557462;178557461	chr2:179422190;179422189;179422188
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-101
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3073
• 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
S/I	None	None	0.971	N	0.703	0.423	0.607230486204	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
S/A	0.1558	likely_benign	0.1914	benign	-0.4	Destabilizing	0.717	D	0.641	neutral	None	None	None	None	I
S/C	0.1072	likely_benign	0.1399	benign	-0.178	Destabilizing	0.997	D	0.639	neutral	N	0.494592056	None	None	I
S/D	0.7661	likely_pathogenic	0.7826	pathogenic	-0.232	Destabilizing	0.754	D	0.621	neutral	None	None	None	None	I
S/E	0.8677	likely_pathogenic	0.8911	pathogenic	-0.334	Destabilizing	0.86	D	0.652	neutral	None	None	None	None	I
S/F	0.4642	ambiguous	0.5648	pathogenic	-1.048	Destabilizing	0.993	D	0.704	prob.neutral	None	None	None	None	I
S/G	0.196	likely_benign	0.2453	benign	-0.499	Destabilizing	0.489	N	0.608	neutral	N	0.479705988	None	None	I
S/H	0.526	ambiguous	0.5931	pathogenic	-1.071	Destabilizing	0.956	D	0.615	neutral	None	None	None	None	I
S/I	0.4319	ambiguous	0.5417	ambiguous	-0.267	Destabilizing	0.971	D	0.703	prob.neutral	N	0.515378882	None	None	I
S/K	0.9172	likely_pathogenic	0.9499	pathogenic	-0.468	Destabilizing	0.754	D	0.653	neutral	None	None	None	None	I
S/L	0.2111	likely_benign	0.269	benign	-0.267	Destabilizing	0.956	D	0.672	neutral	None	None	None	None	I
S/M	0.3176	likely_benign	0.3765	ambiguous	0.185	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	I
S/N	0.2063	likely_benign	0.2516	benign	-0.181	Destabilizing	0.006	N	0.398	neutral	N	0.500895478	None	None	I
S/P	0.9669	likely_pathogenic	0.9744	pathogenic	-0.284	Destabilizing	0.978	D	0.628	neutral	None	None	None	None	I
S/Q	0.7327	likely_pathogenic	0.7997	pathogenic	-0.528	Destabilizing	0.956	D	0.675	neutral	None	None	None	None	I
S/R	0.8779	likely_pathogenic	0.9328	pathogenic	-0.195	Destabilizing	0.942	D	0.631	neutral	N	0.4963988	None	None	I
S/T	0.1713	likely_benign	0.1743	benign	-0.274	Destabilizing	0.822	D	0.621	neutral	N	0.493071118	None	None	I
S/V	0.3853	ambiguous	0.4826	ambiguous	-0.284	Destabilizing	0.978	D	0.699	prob.neutral	None	None	None	None	I
S/W	0.6874	likely_pathogenic	0.7402	pathogenic	-1.037	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	I
S/Y	0.4277	ambiguous	0.4863	ambiguous	-0.758	Destabilizing	0.993	D	0.706	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.