TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19426	58501;58502;58503	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
N2AB	17785	53578;53579;53580	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
N2A	16858	50797;50798;50799	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
N2B	10361	31306;31307;31308	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
Novex-1	10486	31681;31682;31683	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
Novex-2	10553	31882;31883;31884	chr2:178594117;178594116;178594115	chr2:179458844;179458843;179458842
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-118
• Domain position: 36
• Structural Position: 56
• Q(SASA): 0.8664
• 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/H	rs1408473678	None	0.794	D	0.359	0.276	0.406531046227	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93874E-04	None	0	0	0	0	0
D/H	rs1408473678	None	0.794	D	0.359	0.276	0.406531046227	gnomAD-4.0.0	6.57549E-06	None	None	None	None	N	None	0	0	None	0	1.93874E-04	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
D/A	0.0712	likely_benign	0.0648	benign	-0.375	Destabilizing	0.101	N	0.385	neutral	N	0.492058284	None	None	N
D/C	0.3404	ambiguous	0.2808	benign	-0.194	Destabilizing	0.983	D	0.357	neutral	None	None	None	None	N
D/E	0.0815	likely_benign	0.0739	benign	-0.263	Destabilizing	None	N	0.186	neutral	N	0.389931206	None	None	N
D/F	0.3333	likely_benign	0.2657	benign	-0.025	Destabilizing	0.836	D	0.367	neutral	None	None	None	None	N
D/G	0.1074	likely_benign	0.092	benign	-0.608	Destabilizing	0.351	N	0.341	neutral	D	0.528288443	None	None	N
D/H	0.1445	likely_benign	0.1217	benign	0.241	Stabilizing	0.794	D	0.359	neutral	D	0.528115084	None	None	N
D/I	0.138	likely_benign	0.1133	benign	0.207	Stabilizing	0.264	N	0.375	neutral	None	None	None	None	N
D/K	0.1205	likely_benign	0.1022	benign	0.26	Stabilizing	0.129	N	0.347	neutral	None	None	None	None	N
D/L	0.1485	likely_benign	0.1288	benign	0.207	Stabilizing	0.129	N	0.383	neutral	None	None	None	None	N
D/M	0.2922	likely_benign	0.2405	benign	0.228	Stabilizing	0.836	D	0.361	neutral	None	None	None	None	N
D/N	0.0708	likely_benign	0.066	benign	-0.265	Destabilizing	0.351	N	0.307	neutral	N	0.492751717	None	None	N
D/P	0.1968	likely_benign	0.1622	benign	0.035	Stabilizing	0.593	D	0.372	neutral	None	None	None	None	N
D/Q	0.1491	likely_benign	0.1244	benign	-0.188	Destabilizing	0.264	N	0.275	neutral	None	None	None	None	N
D/R	0.1589	likely_benign	0.1261	benign	0.549	Stabilizing	0.418	N	0.368	neutral	None	None	None	None	N
D/S	0.0798	likely_benign	0.0717	benign	-0.366	Destabilizing	0.129	N	0.308	neutral	None	None	None	None	N
D/T	0.1121	likely_benign	0.0973	benign	-0.169	Destabilizing	0.01	N	0.191	neutral	None	None	None	None	N
D/V	0.0861	likely_benign	0.0734	benign	0.035	Stabilizing	0.002	N	0.281	neutral	N	0.459351219	None	None	N
D/W	0.7044	likely_pathogenic	0.6179	pathogenic	0.201	Stabilizing	0.983	D	0.393	neutral	None	None	None	None	N
D/Y	0.1327	likely_benign	0.1178	benign	0.239	Stabilizing	0.921	D	0.368	neutral	N	0.497381938	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.