TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28298	85117;85118;85119	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
N2AB	26657	80194;80195;80196	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
N2A	25730	77413;77414;77415	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
N2B	19233	57922;57923;57924	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
Novex-1	19358	58297;58298;58299	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
Novex-2	19425	58498;58499;58500	chr2:178561240;178561239;178561238	chr2:179425967;179425966;179425965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-94
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.787
• 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
R/L	rs187270666	None	0.987	N	0.459	0.438	0.472504041403	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs187270666	None	0.987	N	0.459	0.438	0.472504041403	gnomAD-4.0.0	1.23952E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69519E-06	0	0
R/Q	None	0.166	0.959	N	0.48	0.218	None	gnomAD-2.1.1	1.44735E-03	None	None	None	None	N	None	8.27E-05	0	None	0	1.54321E-04	None	1.30727E-04	None	1.19907E-02	6.56897E-04	1.82584E-03
R/Q	None	0.166	0.959	N	0.48	0.218	None	gnomAD-3.1.2	1.1505E-03	None	None	None	None	N	None	7.24E-05	6.55E-05	0	0	1.93349E-04	None	1.33786E-02	0	3.82297E-04	4.14079E-04	0
R/Q	None	0.166	0.959	N	0.48	0.218	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	0	2E-03	None	None	None	1E-03	None
R/Q	None	0.166	0.959	N	0.48	0.218	None	gnomAD-4.0.0	6.59377E-04	None	None	None	None	N	None	5.33134E-05	1.66661E-05	None	0	2.00902E-04	None	1.1973E-02	0	1.93253E-04	8.78349E-05	7.84326E-04
R/W	rs779581886	-0.405	1.0	N	0.672	0.428	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	1.29182E-04	0	None	0	5.59E-05	None	0	None	4.65E-05	8.89E-06	0
R/W	rs779581886	-0.405	1.0	N	0.672	0.428	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/W	rs779581886	-0.405	1.0	N	0.672	0.428	None	gnomAD-4.0.0	9.9164E-06	None	None	None	None	N	None	5.3416E-05	0	None	0	2.23135E-05	None	1.56495E-05	0	6.78079E-06	2.19616E-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
R/A	0.8674	likely_pathogenic	0.854	pathogenic	0.06	Stabilizing	0.916	D	0.517	neutral	None	None	None	None	N
R/C	0.4752	ambiguous	0.4517	ambiguous	-0.33	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
R/D	0.9348	likely_pathogenic	0.926	pathogenic	-0.297	Destabilizing	0.845	D	0.45	neutral	None	None	None	None	N
R/E	0.7821	likely_pathogenic	0.7503	pathogenic	-0.247	Destabilizing	0.033	N	0.413	neutral	None	None	None	None	N
R/F	0.8546	likely_pathogenic	0.8548	pathogenic	-0.264	Destabilizing	0.996	D	0.613	neutral	None	None	None	None	N
R/G	0.7782	likely_pathogenic	0.763	pathogenic	-0.086	Destabilizing	0.954	D	0.443	neutral	N	0.511302113	None	None	N
R/H	0.2184	likely_benign	0.2049	benign	-0.59	Destabilizing	0.987	D	0.526	neutral	None	None	None	None	N
R/I	0.6681	likely_pathogenic	0.6308	pathogenic	0.401	Stabilizing	0.987	D	0.627	neutral	None	None	None	None	N
R/K	0.2389	likely_benign	0.2161	benign	-0.181	Destabilizing	0.693	D	0.545	neutral	None	None	None	None	N
R/L	0.6168	likely_pathogenic	0.5909	pathogenic	0.401	Stabilizing	0.987	D	0.459	neutral	N	0.465012455	None	None	N
R/M	0.7303	likely_pathogenic	0.7109	pathogenic	-0.116	Destabilizing	0.999	D	0.511	neutral	None	None	None	None	N
R/N	0.8727	likely_pathogenic	0.8647	pathogenic	-0.179	Destabilizing	0.975	D	0.479	neutral	None	None	None	None	N
R/P	0.8814	likely_pathogenic	0.8673	pathogenic	0.306	Stabilizing	0.993	D	0.555	neutral	N	0.479179918	None	None	N
R/Q	0.2465	likely_benign	0.2222	benign	-0.179	Destabilizing	0.959	D	0.48	neutral	N	0.517382724	None	None	N
R/S	0.8958	likely_pathogenic	0.889	pathogenic	-0.344	Destabilizing	0.916	D	0.473	neutral	None	None	None	None	N
R/T	0.7688	likely_pathogenic	0.7401	pathogenic	-0.18	Destabilizing	0.975	D	0.462	neutral	None	None	None	None	N
R/V	0.7711	likely_pathogenic	0.7416	pathogenic	0.306	Stabilizing	0.987	D	0.625	neutral	None	None	None	None	N
R/W	0.4434	ambiguous	0.4385	ambiguous	-0.461	Destabilizing	1.0	D	0.672	neutral	N	0.512034293	None	None	N
R/Y	0.6782	likely_pathogenic	0.6741	pathogenic	-0.043	Destabilizing	0.996	D	0.558	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.