TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21353	64282;64283;64284	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
N2AB	19712	59359;59360;59361	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
N2A	18785	56578;56579;56580	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
N2B	12288	37087;37088;37089	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
Novex-1	12413	37462;37463;37464	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
Novex-2	12480	37663;37664;37665	chr2:178587154;178587153;178587152	chr2:179451881;179451880;179451879
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: Fn3-42
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.4813
• 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	0.392	N	0.813	0.2	0.202086224978	gnomAD-4.0.0	6.84395E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99709E-07	0	0
D/V	None	None	0.693	N	0.789	0.23	0.523133305157	gnomAD-4.0.0	3.42198E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59884E-06	0	1.65728E-05

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	0.138	likely_benign	0.1416	benign	-0.106	Destabilizing	0.244	N	0.82	deleterious	N	0.47026078	None	None	N
D/C	0.4759	ambiguous	0.4985	ambiguous	-0.094	Destabilizing	0.986	D	0.833	deleterious	None	None	None	None	N
D/E	0.1018	likely_benign	0.1249	benign	-0.562	Destabilizing	0.002	N	0.32	neutral	N	0.378812057	None	None	N
D/F	0.4606	ambiguous	0.5011	ambiguous	0.614	Stabilizing	0.986	D	0.877	deleterious	None	None	None	None	N
D/G	0.2276	likely_benign	0.2494	benign	-0.53	Destabilizing	0.392	N	0.813	deleterious	N	0.509800603	None	None	N
D/H	0.2928	likely_benign	0.3048	benign	0.268	Stabilizing	0.945	D	0.844	deleterious	N	0.509973962	None	None	N
D/I	0.2212	likely_benign	0.23	benign	1.032	Stabilizing	0.858	D	0.853	deleterious	None	None	None	None	N
D/K	0.441	ambiguous	0.4678	ambiguous	-0.399	Destabilizing	0.6	D	0.827	deleterious	None	None	None	None	N
D/L	0.2786	likely_benign	0.2892	benign	1.032	Stabilizing	0.749	D	0.781	deleterious	None	None	None	None	N
D/M	0.4125	ambiguous	0.4485	ambiguous	1.356	Stabilizing	0.986	D	0.869	deleterious	None	None	None	None	N
D/N	0.1128	likely_benign	0.1127	benign	-0.938	Destabilizing	0.693	D	0.855	deleterious	N	0.497602097	None	None	N
D/P	0.619	likely_pathogenic	0.6231	pathogenic	0.68	Stabilizing	0.858	D	0.821	deleterious	None	None	None	None	N
D/Q	0.3092	likely_benign	0.3453	ambiguous	-0.691	Destabilizing	0.6	D	0.831	deleterious	None	None	None	None	N
D/R	0.4902	ambiguous	0.508	ambiguous	-0.191	Destabilizing	0.6	D	0.792	deleterious	None	None	None	None	N
D/S	0.1198	likely_benign	0.1228	benign	-1.255	Destabilizing	0.299	N	0.804	deleterious	None	None	None	None	N
D/T	0.1739	likely_benign	0.1788	benign	-0.896	Destabilizing	0.749	D	0.747	deleterious	None	None	None	None	N
D/V	0.1339	likely_benign	0.1382	benign	0.68	Stabilizing	0.693	D	0.789	deleterious	N	0.47362916	None	None	N
D/W	0.8332	likely_pathogenic	0.8578	pathogenic	0.726	Stabilizing	0.986	D	0.817	deleterious	None	None	None	None	N
D/Y	0.2173	likely_benign	0.2305	benign	0.849	Stabilizing	0.981	D	0.878	deleterious	N	0.516881291	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.