TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7656	23191;23192;23193	chr2:178721053;178721052;178721051	chr2:179585780;179585779;179585778
N2AB	7339	22240;22241;22242	chr2:178721053;178721052;178721051	chr2:179585780;179585779;179585778
N2A	6412	19459;19460;19461	chr2:178721053;178721052;178721051	chr2:179585780;179585779;179585778
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-61
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.5426
• 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
N/D	rs184123332	-0.716	0.116	N	0.235	0.193	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	I	None	0	0	None	0	1.66963E-04	None	6.54E-05	None	0	0	0
N/D	rs184123332	-0.716	0.116	N	0.235	0.193	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	7.71903E-04	None	0	0	0	0	0
N/D	rs184123332	-0.716	0.116	N	0.235	0.193	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	1E-03	0	None	None	None	0	None
N/D	rs184123332	-0.716	0.116	N	0.235	0.193	None	gnomAD-4.0.0	8.73922E-05	None	None	None	None	I	None	0	0	None	0	3.09839E-03	None	0	0	0	2.19679E-05	0
N/K	None	None	0.001	N	0.08	0.168	0.17948927462	gnomAD-4.0.0	6.84423E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65733E-05
N/S	rs1197475799	-0.097	0.002	N	0.1	0.092	0.165133752707	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs1197475799	-0.097	0.002	N	0.1	0.092	0.165133752707	gnomAD-4.0.0	1.59231E-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
N/A	0.1394	likely_benign	0.1515	benign	-0.417	Destabilizing	0.036	N	0.272	neutral	None	None	None	None	I
N/C	0.244	likely_benign	0.2346	benign	0.035	Stabilizing	0.901	D	0.361	neutral	None	None	None	None	I
N/D	0.0989	likely_benign	0.1088	benign	-1.447	Destabilizing	0.116	N	0.235	neutral	N	0.45738835	None	None	I
N/E	0.1819	likely_benign	0.2232	benign	-1.388	Destabilizing	0.036	N	0.204	neutral	None	None	None	None	I
N/F	0.377	ambiguous	0.4317	ambiguous	-0.624	Destabilizing	0.296	N	0.437	neutral	None	None	None	None	I
N/G	0.1899	likely_benign	0.2113	benign	-0.685	Destabilizing	0.08	N	0.259	neutral	None	None	None	None	I
N/H	0.0572	likely_benign	0.0594	benign	-0.697	Destabilizing	0.001	N	0.159	neutral	N	0.440400099	None	None	I
N/I	0.1607	likely_benign	0.1674	benign	0.231	Stabilizing	0.001	N	0.304	neutral	N	0.441650893	None	None	I
N/K	0.0996	likely_benign	0.1236	benign	-0.047	Destabilizing	0.001	N	0.08	neutral	N	0.351970251	None	None	I
N/L	0.181	likely_benign	0.1882	benign	0.231	Stabilizing	0.001	N	0.261	neutral	None	None	None	None	I
N/M	0.249	likely_benign	0.2656	benign	0.83	Stabilizing	0.596	D	0.377	neutral	None	None	None	None	I
N/P	0.7096	likely_pathogenic	0.798	pathogenic	0.044	Stabilizing	0.46	N	0.394	neutral	None	None	None	None	I
N/Q	0.127	likely_benign	0.1512	benign	-0.997	Destabilizing	0.007	N	0.079	neutral	None	None	None	None	I
N/R	0.0962	likely_benign	0.1249	benign	0.082	Stabilizing	0.08	N	0.188	neutral	None	None	None	None	I
N/S	0.0635	likely_benign	0.0669	benign	-0.631	Destabilizing	0.002	N	0.1	neutral	N	0.41900332	None	None	I
N/T	0.0895	likely_benign	0.0915	benign	-0.419	Destabilizing	0.061	N	0.225	neutral	N	0.395262455	None	None	I
N/V	0.1667	likely_benign	0.1707	benign	0.044	Stabilizing	0.08	N	0.335	neutral	None	None	None	None	I
N/W	0.5295	ambiguous	0.6294	pathogenic	-0.535	Destabilizing	0.972	D	0.38	neutral	None	None	None	None	I
N/Y	0.1212	likely_benign	0.1365	benign	-0.178	Destabilizing	0.241	N	0.436	neutral	N	0.475128748	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.