TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13926	42001;42002;42003	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
N2AB	12285	37078;37079;37080	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
N2A	11358	34297;34298;34299	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
N2B	4861	14806;14807;14808	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
Novex-1	4986	15181;15182;15183	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
Novex-2	5053	15382;15383;15384	chr2:178635548;178635547;178635546	chr2:179500275;179500274;179500273
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-89
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.492
• 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
D/G	None	None	0.189	N	0.51	0.27	0.188950314367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
D/N	rs2060332594	None	0.449	N	0.558	0.247	0.195762928549	gnomAD-4.0.0	2.56338E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.35837E-05	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
D/A	0.2377	likely_benign	0.2486	benign	-0.253	Destabilizing	0.104	N	0.468	neutral	N	0.509779553	None	None	N
D/C	0.7788	likely_pathogenic	0.7973	pathogenic	-0.114	Destabilizing	0.962	D	0.59	neutral	None	None	None	None	N
D/E	0.1015	likely_benign	0.1101	benign	-0.18	Destabilizing	None	N	0.251	neutral	N	0.444509038	None	None	N
D/F	0.7264	likely_pathogenic	0.7547	pathogenic	-0.14	Destabilizing	0.962	D	0.603	neutral	None	None	None	None	N
D/G	0.3454	ambiguous	0.3553	ambiguous	-0.445	Destabilizing	0.189	N	0.51	neutral	N	0.507833111	None	None	N
D/H	0.449	ambiguous	0.4387	ambiguous	0.184	Stabilizing	0.862	D	0.514	neutral	N	0.511635527	None	None	N
D/I	0.4235	ambiguous	0.4674	ambiguous	0.204	Stabilizing	0.687	D	0.625	neutral	None	None	None	None	N
D/K	0.4197	ambiguous	0.4175	ambiguous	0.164	Stabilizing	0.134	N	0.507	neutral	None	None	None	None	N
D/L	0.5288	ambiguous	0.5717	pathogenic	0.204	Stabilizing	0.519	D	0.645	neutral	None	None	None	None	N
D/M	0.6478	likely_pathogenic	0.7007	pathogenic	0.205	Stabilizing	0.962	D	0.637	neutral	None	None	None	None	N
D/N	0.1606	likely_benign	0.1581	benign	-0.043	Destabilizing	0.449	N	0.558	neutral	N	0.50280466	None	None	N
D/P	0.94	likely_pathogenic	0.9475	pathogenic	0.073	Stabilizing	0.687	D	0.535	neutral	None	None	None	None	N
D/Q	0.3381	likely_benign	0.3455	ambiguous	-0.004	Destabilizing	0.351	N	0.553	neutral	None	None	None	None	N
D/R	0.534	ambiguous	0.514	ambiguous	0.448	Stabilizing	0.351	N	0.538	neutral	None	None	None	None	N
D/S	0.1793	likely_benign	0.18	benign	-0.209	Destabilizing	0.134	N	0.487	neutral	None	None	None	None	N
D/T	0.3013	likely_benign	0.34	benign	-0.06	Destabilizing	0.519	D	0.55	neutral	None	None	None	None	N
D/V	0.2448	likely_benign	0.2749	benign	0.073	Stabilizing	0.449	N	0.664	prob.neutral	N	0.442347604	None	None	N
D/W	0.9163	likely_pathogenic	0.9195	pathogenic	-0.012	Destabilizing	0.962	D	0.583	neutral	None	None	None	None	N
D/Y	0.3834	ambiguous	0.3731	ambiguous	0.093	Stabilizing	0.95	D	0.604	neutral	N	0.51183731	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.