TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22047	66364;66365;66366	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
N2AB	20406	61441;61442;61443	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
N2A	19479	58660;58661;58662	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
N2B	12982	39169;39170;39171	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
Novex-1	13107	39544;39545;39546	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
Novex-2	13174	39745;39746;39747	chr2:178582317;178582316;178582315	chr2:179447044;179447043;179447042
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-47
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.2227
• 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
A/S	None	None	0.361	N	0.54	0.082	0.29132392195	gnomAD-4.0.0	1.65944E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89689E-05	0	0	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
A/C	0.3245	likely_benign	0.2547	benign	-0.757	Destabilizing	0.842	D	0.593	neutral	None	None	None	None	N
A/D	0.5868	likely_pathogenic	0.417	ambiguous	-1.447	Destabilizing	0.842	D	0.68	prob.neutral	None	None	None	None	N
A/E	0.387	ambiguous	0.2689	benign	-1.4	Destabilizing	0.361	N	0.621	neutral	N	0.480971711	None	None	N
A/F	0.3653	ambiguous	0.2449	benign	-0.832	Destabilizing	0.724	D	0.667	prob.neutral	None	None	None	None	N
A/G	0.2272	likely_benign	0.1727	benign	-1.241	Destabilizing	0.534	D	0.549	neutral	N	0.511294618	None	None	N
A/H	0.5331	ambiguous	0.396	ambiguous	-1.393	Destabilizing	0.953	D	0.589	neutral	None	None	None	None	N
A/I	0.1722	likely_benign	0.1167	benign	-0.131	Destabilizing	0.01	N	0.367	neutral	None	None	None	None	N
A/K	0.558	ambiguous	0.3779	ambiguous	-1.271	Destabilizing	0.272	N	0.605	neutral	None	None	None	None	N
A/L	0.1823	likely_benign	0.1293	benign	-0.131	Destabilizing	0.063	N	0.503	neutral	None	None	None	None	N
A/M	0.1884	likely_benign	0.1338	benign	-0.104	Destabilizing	0.724	D	0.663	prob.neutral	None	None	None	None	N
A/N	0.4167	ambiguous	0.2868	benign	-1.136	Destabilizing	0.724	D	0.669	prob.neutral	None	None	None	None	N
A/P	0.9458	likely_pathogenic	0.9123	pathogenic	-0.349	Destabilizing	0.924	D	0.707	prob.delet.	N	0.492612857	None	None	N
A/Q	0.3607	ambiguous	0.2603	benign	-1.188	Destabilizing	0.724	D	0.697	prob.delet.	None	None	None	None	N
A/R	0.5066	ambiguous	0.3507	ambiguous	-0.983	Destabilizing	0.002	N	0.427	neutral	None	None	None	None	N
A/S	0.1222	likely_benign	0.1033	benign	-1.495	Destabilizing	0.361	N	0.54	neutral	N	0.466367618	None	None	N
A/T	0.0813	likely_benign	0.0668	benign	-1.342	Destabilizing	0.189	N	0.497	neutral	N	0.461519159	None	None	N
A/V	0.0892	likely_benign	0.069	benign	-0.349	Destabilizing	None	N	0.167	neutral	N	0.356023703	None	None	N
A/W	0.8046	likely_pathogenic	0.6847	pathogenic	-1.322	Destabilizing	0.984	D	0.724	deleterious	None	None	None	None	N
A/Y	0.5268	ambiguous	0.3843	ambiguous	-0.843	Destabilizing	0.842	D	0.627	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.