TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16161	48706;48707;48708	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
N2AB	14520	43783;43784;43785	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
N2A	13593	41002;41003;41004	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
N2B	7096	21511;21512;21513	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
Novex-1	7221	21886;21887;21888	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
Novex-2	7288	22087;22088;22089	chr2:178615464;178615463;178615462	chr2:179480191;179480190;179480189
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: Fn3-5
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6229
• 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	rs755404483	0.27	0.999	N	0.581	0.449	0.318828661733	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
N/S	rs755404483	0.27	0.999	N	0.581	0.449	0.318828661733	gnomAD-4.0.0	1.59481E-06	None	None	None	None	N	None	0	2.28917E-05	None	0	0	None	0	0	0	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	0.4908	ambiguous	0.4802	ambiguous	-0.302	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
N/C	0.6011	likely_pathogenic	0.6161	pathogenic	0.34	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
N/D	0.3474	ambiguous	0.3107	benign	-0.005	Destabilizing	0.999	D	0.618	neutral	N	0.48483599	None	None	N
N/E	0.7068	likely_pathogenic	0.6722	pathogenic	-0.039	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
N/F	0.7521	likely_pathogenic	0.7571	pathogenic	-0.615	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
N/G	0.502	ambiguous	0.5058	ambiguous	-0.484	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
N/H	0.2353	likely_benign	0.2349	benign	-0.499	Destabilizing	1.0	D	0.627	neutral	D	0.583296942	None	None	N
N/I	0.6165	likely_pathogenic	0.5848	pathogenic	0.089	Stabilizing	1.0	D	0.729	prob.delet.	D	0.641439004	None	None	N
N/K	0.5717	likely_pathogenic	0.5274	ambiguous	0.012	Stabilizing	1.0	D	0.702	prob.neutral	N	0.517607626	None	None	N
N/L	0.6008	likely_pathogenic	0.5861	pathogenic	0.089	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/M	0.579	likely_pathogenic	0.567	pathogenic	0.413	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
N/P	0.9796	likely_pathogenic	0.9622	pathogenic	-0.014	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
N/Q	0.5724	likely_pathogenic	0.5676	pathogenic	-0.414	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/R	0.6418	likely_pathogenic	0.5978	pathogenic	0.086	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
N/S	0.2535	likely_benign	0.2529	benign	-0.17	Destabilizing	0.999	D	0.581	neutral	N	0.482384889	None	None	N
N/T	0.3868	ambiguous	0.3574	ambiguous	-0.067	Destabilizing	0.999	D	0.689	prob.neutral	N	0.509160026	None	None	N
N/V	0.5818	likely_pathogenic	0.5635	ambiguous	-0.014	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/W	0.9356	likely_pathogenic	0.9299	pathogenic	-0.595	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/Y	0.3189	likely_benign	0.3151	benign	-0.343	Destabilizing	1.0	D	0.703	prob.neutral	D	0.731133598	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.