TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21983	66172;66173;66174	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
N2AB	20342	61249;61250;61251	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
N2A	19415	58468;58469;58470	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
N2B	12918	38977;38978;38979	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
Novex-1	13043	39352;39353;39354	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
Novex-2	13110	39553;39554;39555	chr2:178582509;178582508;178582507	chr2:179447236;179447235;179447234
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-47
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3099
• 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
D/N	rs2048004611	None	0.467	N	0.255	0.323	0.32082282376	gnomAD-4.0.0	1.59314E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43357E-05	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
D/A	0.8749	likely_pathogenic	0.8221	pathogenic	-0.26	Destabilizing	0.998	D	0.619	neutral	N	0.499476673	None	None	I
D/C	0.9858	likely_pathogenic	0.9731	pathogenic	0.198	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	I
D/E	0.8925	likely_pathogenic	0.8462	pathogenic	-0.565	Destabilizing	0.992	D	0.451	neutral	N	0.5089961	None	None	I
D/F	0.9824	likely_pathogenic	0.975	pathogenic	-0.458	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
D/G	0.8408	likely_pathogenic	0.8062	pathogenic	-0.497	Destabilizing	0.992	D	0.597	neutral	N	0.513506005	None	None	I
D/H	0.9475	likely_pathogenic	0.9137	pathogenic	-0.765	Destabilizing	1.0	D	0.698	prob.neutral	N	0.52048099	None	None	I
D/I	0.9599	likely_pathogenic	0.94	pathogenic	0.322	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
D/K	0.9683	likely_pathogenic	0.9524	pathogenic	0.175	Stabilizing	0.998	D	0.635	neutral	None	None	None	None	I
D/L	0.9586	likely_pathogenic	0.9385	pathogenic	0.322	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	I
D/M	0.9803	likely_pathogenic	0.9686	pathogenic	0.732	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	I
D/N	0.3089	likely_benign	0.2479	benign	-0.076	Destabilizing	0.467	N	0.255	neutral	N	0.481296739	None	None	I
D/P	0.9826	likely_pathogenic	0.9721	pathogenic	0.152	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
D/Q	0.9667	likely_pathogenic	0.9454	pathogenic	-0.027	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	I
D/R	0.9777	likely_pathogenic	0.9643	pathogenic	0.094	Stabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	I
D/S	0.688	likely_pathogenic	0.5981	pathogenic	-0.194	Destabilizing	0.988	D	0.605	neutral	None	None	None	None	I
D/T	0.7899	likely_pathogenic	0.7545	pathogenic	-0.007	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	I
D/V	0.9072	likely_pathogenic	0.8769	pathogenic	0.152	Stabilizing	0.999	D	0.659	neutral	D	0.534951168	None	None	I
D/W	0.9968	likely_pathogenic	0.9945	pathogenic	-0.434	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
D/Y	0.8859	likely_pathogenic	0.8334	pathogenic	-0.247	Destabilizing	1.0	D	0.651	neutral	D	0.536218615	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.