TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7383	22372;22373;22374	chr2:178722752;178722751;178722750	chr2:179587479;179587478;179587477
N2AB	7066	21421;21422;21423	chr2:178722752;178722751;178722750	chr2:179587479;179587478;179587477
N2A	6139	18640;18641;18642	chr2:178722752;178722751;178722750	chr2:179587479;179587478;179587477
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: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-58
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.6571
• 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
N/S	rs562295146	-0.33	0.003	N	0.093	0.151	0.180583059064	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	4.14E-05	2.84E-05	None	0	0	None	0	None	0	7.84E-06	0
N/S	rs562295146	-0.33	0.003	N	0.093	0.151	0.180583059064	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	2.41E-05	3.27568E-04	0	0	0	None	0	0	1.47E-05	0	0
N/S	rs562295146	-0.33	0.003	N	0.093	0.151	0.180583059064	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	1E-03	None	None	None	0	None
N/S	rs562295146	-0.33	0.003	N	0.093	0.151	0.180583059064	gnomAD-4.0.0	1.02536E-05	None	None	None	None	N	None	1.68782E-05	8.47831E-05	None	0	0	None	0	0	4.789E-06	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
N/A	0.1811	likely_benign	0.261	benign	-0.694	Destabilizing	0.001	N	0.15	neutral	None	None	None	None	N
N/C	0.2541	likely_benign	0.3544	ambiguous	0.145	Stabilizing	0.995	D	0.365	neutral	None	None	None	None	N
N/D	0.1434	likely_benign	0.2148	benign	-0.025	Destabilizing	0.366	N	0.232	neutral	N	0.478819627	None	None	N
N/E	0.3441	ambiguous	0.4889	ambiguous	-0.002	Destabilizing	0.513	D	0.222	neutral	None	None	None	None	N
N/F	0.4598	ambiguous	0.6103	pathogenic	-0.75	Destabilizing	0.971	D	0.421	neutral	None	None	None	None	N
N/G	0.1769	likely_benign	0.242	benign	-0.95	Destabilizing	0.57	D	0.235	neutral	None	None	None	None	N
N/H	0.0783	likely_benign	0.0905	benign	-0.819	Destabilizing	0.019	N	0.178	neutral	N	0.472125729	None	None	N
N/I	0.2257	likely_benign	0.3337	benign	-0.082	Destabilizing	0.574	D	0.452	neutral	N	0.499234972	None	None	N
N/K	0.241	likely_benign	0.3634	ambiguous	-0.01	Destabilizing	0.598	D	0.239	neutral	N	0.466813122	None	None	N
N/L	0.1879	likely_benign	0.2465	benign	-0.082	Destabilizing	0.011	N	0.237	neutral	None	None	None	None	N
N/M	0.3168	likely_benign	0.4191	ambiguous	0.399	Stabilizing	0.926	D	0.378	neutral	None	None	None	None	N
N/P	0.259	likely_benign	0.3267	benign	-0.257	Destabilizing	0.845	D	0.419	neutral	None	None	None	None	N
N/Q	0.232	likely_benign	0.3159	benign	-0.603	Destabilizing	0.781	D	0.267	neutral	None	None	None	None	N
N/R	0.2254	likely_benign	0.3436	ambiguous	0.032	Stabilizing	0.029	N	0.165	neutral	None	None	None	None	N
N/S	0.0637	likely_benign	0.0687	benign	-0.493	Destabilizing	0.003	N	0.093	neutral	N	0.419059248	None	None	N
N/T	0.1084	likely_benign	0.1446	benign	-0.292	Destabilizing	0.156	N	0.236	neutral	N	0.471624296	None	None	N
N/V	0.232	likely_benign	0.342	ambiguous	-0.257	Destabilizing	0.13	N	0.433	neutral	None	None	None	None	N
N/W	0.6454	likely_pathogenic	0.7621	pathogenic	-0.541	Destabilizing	0.999	D	0.396	neutral	None	None	None	None	N
N/Y	0.1465	likely_benign	0.1985	benign	-0.334	Destabilizing	0.962	D	0.399	neutral	N	0.481918648	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.