TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8236	24931;24932;24933	chr2:178718400;178718399;178718398	chr2:179583127;179583126;179583125
N2AB	7919	23980;23981;23982	chr2:178718400;178718399;178718398	chr2:179583127;179583126;179583125
N2A	6992	21199;21200;21201	chr2:178718400;178718399;178718398	chr2:179583127;179583126;179583125
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-67
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.5878
• 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
E/K	rs377762626	0.7	0.505	N	0.46	0.214	None	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	3.56E-05	0
E/K	rs377762626	0.7	0.505	N	0.46	0.214	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06782E-04	0
E/K	rs377762626	0.7	0.505	N	0.46	0.214	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/K	rs377762626	0.7	0.505	N	0.46	0.214	None	gnomAD-4.0.0	1.09475E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07938E-05	4.63736E-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
E/A	0.1424	likely_benign	0.1304	benign	-0.168	Destabilizing	0.174	N	0.457	neutral	N	0.499943395	None	None	N
E/C	0.8411	likely_pathogenic	0.8251	pathogenic	0.08	Stabilizing	0.991	D	0.553	neutral	None	None	None	None	N
E/D	0.0932	likely_benign	0.0873	benign	-0.183	Destabilizing	0.001	N	0.158	neutral	N	0.478778689	None	None	N
E/F	0.7089	likely_pathogenic	0.6968	pathogenic	-0.212	Destabilizing	0.967	D	0.521	neutral	None	None	None	None	N
E/G	0.1338	likely_benign	0.121	benign	-0.31	Destabilizing	0.338	N	0.444	neutral	N	0.456265226	None	None	N
E/H	0.3835	ambiguous	0.3603	ambiguous	0.159	Stabilizing	0.967	D	0.401	neutral	None	None	None	None	N
E/I	0.4385	ambiguous	0.4204	ambiguous	0.151	Stabilizing	0.906	D	0.515	neutral	None	None	None	None	N
E/K	0.1177	likely_benign	0.1084	benign	0.496	Stabilizing	0.505	D	0.46	neutral	N	0.457581899	None	None	N
E/L	0.4104	ambiguous	0.3823	ambiguous	0.151	Stabilizing	0.826	D	0.423	neutral	None	None	None	None	N
E/M	0.4786	ambiguous	0.4531	ambiguous	0.176	Stabilizing	0.991	D	0.496	neutral	None	None	None	None	N
E/N	0.206	likely_benign	0.1869	benign	0.284	Stabilizing	0.404	N	0.405	neutral	None	None	None	None	N
E/P	0.6104	likely_pathogenic	0.5668	pathogenic	0.064	Stabilizing	0.906	D	0.401	neutral	None	None	None	None	N
E/Q	0.1396	likely_benign	0.1297	benign	0.302	Stabilizing	0.505	D	0.431	neutral	N	0.466976422	None	None	N
E/R	0.2003	likely_benign	0.1971	benign	0.634	Stabilizing	0.826	D	0.393	neutral	None	None	None	None	N
E/S	0.157	likely_benign	0.1477	benign	0.131	Stabilizing	0.018	N	0.209	neutral	None	None	None	None	N
E/T	0.1958	likely_benign	0.1803	benign	0.251	Stabilizing	0.404	N	0.419	neutral	None	None	None	None	N
E/V	0.2784	likely_benign	0.2561	benign	0.064	Stabilizing	0.782	D	0.407	neutral	N	0.488816886	None	None	N
E/W	0.8197	likely_pathogenic	0.8012	pathogenic	-0.14	Destabilizing	0.991	D	0.655	neutral	None	None	None	None	N
E/Y	0.5698	likely_pathogenic	0.5408	ambiguous	0.017	Stabilizing	0.967	D	0.499	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.