TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17733	53422;53423;53424	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
N2AB	16092	48499;48500;48501	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
N2A	15165	45718;45719;45720	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
N2B	8668	26227;26228;26229	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
Novex-1	8793	26602;26603;26604	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
Novex-2	8860	26803;26804;26805	chr2:178607491;178607490;178607489	chr2:179472218;179472217;179472216
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-113
• Domain position: 57
• Structural Position: 143
• Q(SASA): 0.5444
• 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/E	None	None	None	N	0.146	0.098	0.101711395817	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.2017	likely_benign	0.1982	benign	-0.533	Destabilizing	0.005	N	0.219	neutral	N	0.474738306	None	None	N
D/C	0.5721	likely_pathogenic	0.6185	pathogenic	-0.003	Destabilizing	0.356	N	0.392	neutral	None	None	None	None	N
D/E	0.1611	likely_benign	0.1301	benign	-0.435	Destabilizing	None	N	0.146	neutral	N	0.439124223	None	None	N
D/F	0.603	likely_pathogenic	0.6103	pathogenic	-0.486	Destabilizing	0.356	N	0.471	neutral	None	None	None	None	N
D/G	0.1543	likely_benign	0.1686	benign	-0.767	Destabilizing	0.005	N	0.219	neutral	N	0.461019648	None	None	N
D/H	0.2385	likely_benign	0.2631	benign	-0.606	Destabilizing	0.171	N	0.359	neutral	N	0.496537731	None	None	N
D/I	0.5393	ambiguous	0.5372	ambiguous	0.051	Stabilizing	0.072	N	0.51	neutral	None	None	None	None	N
D/K	0.3265	likely_benign	0.3586	ambiguous	0.069	Stabilizing	0.016	N	0.287	neutral	None	None	None	None	N
D/L	0.4492	ambiguous	0.4692	ambiguous	0.051	Stabilizing	0.031	N	0.347	neutral	None	None	None	None	N
D/M	0.6184	likely_pathogenic	0.6338	pathogenic	0.422	Stabilizing	0.628	D	0.407	neutral	None	None	None	None	N
D/N	0.0722	likely_benign	0.0757	benign	-0.243	Destabilizing	None	N	0.095	neutral	N	0.420919677	None	None	N
D/P	0.8079	likely_pathogenic	0.8592	pathogenic	-0.121	Destabilizing	0.136	N	0.381	neutral	None	None	None	None	N
D/Q	0.298	likely_benign	0.3005	benign	-0.199	Destabilizing	0.038	N	0.149	neutral	None	None	None	None	N
D/R	0.4124	ambiguous	0.4501	ambiguous	0.147	Stabilizing	0.031	N	0.376	neutral	None	None	None	None	N
D/S	0.1429	likely_benign	0.1521	benign	-0.384	Destabilizing	None	N	0.147	neutral	None	None	None	None	N
D/T	0.2491	likely_benign	0.275	benign	-0.199	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
D/V	0.336	likely_benign	0.3238	benign	-0.121	Destabilizing	0.024	N	0.35	neutral	N	0.461772182	None	None	N
D/W	0.8539	likely_pathogenic	0.876	pathogenic	-0.338	Destabilizing	0.864	D	0.404	neutral	None	None	None	None	N
D/Y	0.1911	likely_benign	0.2134	benign	-0.257	Destabilizing	0.56	D	0.474	neutral	N	0.473276869	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.