TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9335	28228;28229;28230	chr2:178711233;178711232;178711231	chr2:179575960;179575959;179575958
N2AB	9018	27277;27278;27279	chr2:178711233;178711232;178711231	chr2:179575960;179575959;179575958
N2A	8091	24496;24497;24498	chr2:178711233;178711232;178711231	chr2:179575960;179575959;179575958
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-79
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.3222
• 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
Y/C	rs745989523	-0.961	0.427	None	0.526	0.26	0.265010934533	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
Y/C	rs745989523	-0.961	0.427	None	0.526	0.26	0.265010934533	gnomAD-4.0.0	1.59108E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85804E-06	0	0
Y/N	None	None	None	None	0.316	0.279	0.51469891142	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
Y/A	0.4496	ambiguous	0.3754	ambiguous	-2.147	Highly Destabilizing	0.004	N	0.387	neutral	None	None	None	None	N
Y/C	0.2199	likely_benign	0.1748	benign	-0.945	Destabilizing	0.427	N	0.526	neutral	None	None	None	None	N
Y/D	0.3381	likely_benign	0.3057	benign	-0.105	Destabilizing	0.007	N	0.488	neutral	None	None	None	None	N
Y/E	0.493	ambiguous	0.4048	ambiguous	-0.029	Destabilizing	0.009	N	0.453	neutral	None	None	None	None	N
Y/F	0.0725	likely_benign	0.0653	benign	-1.007	Destabilizing	None	N	0.123	neutral	None	None	None	None	N
Y/G	0.4492	ambiguous	0.3795	ambiguous	-2.441	Highly Destabilizing	0.009	N	0.473	neutral	None	None	None	None	N
Y/H	0.1376	likely_benign	0.1118	benign	-0.809	Destabilizing	0.108	N	0.45	neutral	None	None	None	None	N
Y/I	0.3419	ambiguous	0.2783	benign	-1.274	Destabilizing	0.009	N	0.428	neutral	None	None	None	None	N
Y/K	0.4816	ambiguous	0.3781	ambiguous	-0.765	Destabilizing	0.009	N	0.472	neutral	None	None	None	None	N
Y/L	0.3069	likely_benign	0.2519	benign	-1.274	Destabilizing	None	N	0.236	neutral	None	None	None	None	N
Y/M	0.4051	ambiguous	0.3268	benign	-0.977	Destabilizing	0.138	N	0.537	neutral	None	None	None	None	N
Y/N	0.1353	likely_benign	0.1118	benign	-0.907	Destabilizing	None	N	0.316	neutral	None	None	None	None	N
Y/P	0.9873	likely_pathogenic	0.9839	pathogenic	-1.557	Destabilizing	0.085	N	0.579	neutral	None	None	None	None	N
Y/Q	0.3197	likely_benign	0.2439	benign	-0.903	Destabilizing	0.002	N	0.241	neutral	None	None	None	None	N
Y/R	0.3519	ambiguous	0.284	benign	-0.305	Destabilizing	0.044	N	0.569	neutral	None	None	None	None	N
Y/S	0.1489	likely_benign	0.1262	benign	-1.643	Destabilizing	0.001	N	0.305	neutral	None	None	None	None	N
Y/T	0.3031	likely_benign	0.2497	benign	-1.475	Destabilizing	0.009	N	0.458	neutral	None	None	None	None	N
Y/V	0.2875	likely_benign	0.2462	benign	-1.557	Destabilizing	None	N	0.239	neutral	None	None	None	None	N
Y/W	0.4106	ambiguous	0.3762	ambiguous	-0.553	Destabilizing	0.245	N	0.464	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.