TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30569	91930;91931;91932	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
N2AB	28928	87007;87008;87009	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
N2A	28001	84226;84227;84228	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
N2B	21504	64735;64736;64737	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
Novex-1	21629	65110;65111;65112	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
Novex-2	21696	65311;65312;65313	chr2:178550133;178550132;178550131	chr2:179414860;179414859;179414858
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-149
• Domain position: 38
• Structural Position: 70
• Q(SASA): 0.7569
• 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
K/N	rs1060500543	0.365	0.638	N	0.451	0.21	0.337378238328	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/N	rs1060500543	0.365	0.638	N	0.451	0.21	0.337378238328	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1060500543	0.365	0.638	N	0.451	0.21	0.337378238328	gnomAD-4.0.0	9.2954E-06	None	None	None	None	N	None	1.33483E-05	0	None	0	0	None	0	0	1.18665E-05	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
K/A	0.336	likely_benign	0.3965	ambiguous	0.061	Stabilizing	0.25	N	0.485	neutral	None	None	None	None	N
K/C	0.6562	likely_pathogenic	0.6974	pathogenic	-0.376	Destabilizing	0.982	D	0.616	neutral	None	None	None	None	N
K/D	0.4407	ambiguous	0.5026	ambiguous	-0.017	Destabilizing	0.7	D	0.471	neutral	None	None	None	None	N
K/E	0.1726	likely_benign	0.2093	benign	0.012	Stabilizing	0.201	N	0.511	neutral	N	0.435124778	None	None	N
K/F	0.7772	likely_pathogenic	0.825	pathogenic	-0.087	Destabilizing	0.826	D	0.609	neutral	None	None	None	None	N
K/G	0.305	likely_benign	0.3528	ambiguous	-0.145	Destabilizing	0.399	N	0.461	neutral	None	None	None	None	N
K/H	0.2878	likely_benign	0.3221	benign	-0.294	Destabilizing	0.947	D	0.523	neutral	None	None	None	None	N
K/I	0.4811	ambiguous	0.5463	ambiguous	0.531	Stabilizing	0.7	D	0.619	neutral	None	None	None	None	N
K/L	0.3656	ambiguous	0.4189	ambiguous	0.531	Stabilizing	0.25	N	0.469	neutral	None	None	None	None	N
K/M	0.2966	likely_benign	0.3489	ambiguous	0.052	Stabilizing	0.931	D	0.525	neutral	D	0.535214415	None	None	N
K/N	0.3369	likely_benign	0.3919	ambiguous	0.02	Stabilizing	0.638	D	0.451	neutral	N	0.424910572	None	None	N
K/P	0.3925	ambiguous	0.4464	ambiguous	0.402	Stabilizing	0.826	D	0.523	neutral	None	None	None	None	N
K/Q	0.1262	likely_benign	0.1439	benign	-0.059	Destabilizing	0.638	D	0.501	neutral	N	0.491191492	None	None	N
K/R	0.078	likely_benign	0.0816	benign	-0.098	Destabilizing	0.004	N	0.347	neutral	N	0.496906743	None	None	N
K/S	0.3516	ambiguous	0.4134	ambiguous	-0.394	Destabilizing	0.25	N	0.503	neutral	None	None	None	None	N
K/T	0.206	likely_benign	0.2424	benign	-0.214	Destabilizing	0.004	N	0.355	neutral	N	0.460023223	None	None	N
K/V	0.4062	ambiguous	0.4683	ambiguous	0.402	Stabilizing	0.539	D	0.444	neutral	None	None	None	None	N
K/W	0.6808	likely_pathogenic	0.728	pathogenic	-0.166	Destabilizing	0.982	D	0.647	neutral	None	None	None	None	N
K/Y	0.5775	likely_pathogenic	0.6318	pathogenic	0.191	Stabilizing	0.826	D	0.579	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.