TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4893	14902;14903;14904	chr2:178735769;178735768;178735767	chr2:179600496;179600495;179600494
N2AB	4576	13951;13952;13953	chr2:178735769;178735768;178735767	chr2:179600496;179600495;179600494
N2A	3649	11170;11171;11172	chr2:178735769;178735768;178735767	chr2:179600496;179600495;179600494
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-32
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.7468
• 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
E/D	rs761383226	0.021	None	D	0.149	0.162	0.130388298395	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/D	rs761383226	0.021	None	D	0.149	0.162	0.130388298395	gnomAD-4.0.0	9.549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.59673E-05	0
E/K	None	None	0.012	N	0.235	0.113	0.267755039894	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99468E-07	0	0
E/Q	None	None	None	N	0.151	0.084	0.226586394389	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99468E-07	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
E/A	0.1026	likely_benign	0.0942	benign	-0.735	Destabilizing	None	N	0.13	neutral	N	0.504899869	None	None	N
E/C	0.7161	likely_pathogenic	0.6513	pathogenic	-0.404	Destabilizing	0.864	D	0.272	neutral	None	None	None	None	N
E/D	0.1488	likely_benign	0.1395	benign	-0.676	Destabilizing	None	N	0.149	neutral	D	0.566677304	None	None	N
E/F	0.6027	likely_pathogenic	0.5385	ambiguous	-0.084	Destabilizing	0.356	N	0.304	neutral	None	None	None	None	N
E/G	0.1045	likely_benign	0.0958	benign	-1.058	Destabilizing	0.024	N	0.337	neutral	N	0.513098491	None	None	N
E/H	0.3567	ambiguous	0.3088	benign	-0.115	Destabilizing	0.214	N	0.296	neutral	None	None	None	None	N
E/I	0.2705	likely_benign	0.2297	benign	0.134	Stabilizing	0.038	N	0.4	neutral	None	None	None	None	N
E/K	0.0995	likely_benign	0.0835	benign	-0.245	Destabilizing	0.012	N	0.235	neutral	N	0.464025891	None	None	N
E/L	0.2676	likely_benign	0.2212	benign	0.134	Stabilizing	0.016	N	0.342	neutral	None	None	None	None	N
E/M	0.3062	likely_benign	0.2656	benign	0.359	Stabilizing	0.356	N	0.289	neutral	None	None	None	None	N
E/N	0.2039	likely_benign	0.1708	benign	-0.757	Destabilizing	0.038	N	0.243	neutral	None	None	None	None	N
E/P	0.2458	likely_benign	0.2298	benign	-0.135	Destabilizing	None	N	0.228	neutral	None	None	None	None	N
E/Q	0.1003	likely_benign	0.0905	benign	-0.639	Destabilizing	None	N	0.151	neutral	N	0.500518501	None	None	N
E/R	0.169	likely_benign	0.1445	benign	0.112	Stabilizing	0.038	N	0.275	neutral	None	None	None	None	N
E/S	0.1569	likely_benign	0.138	benign	-1.015	Destabilizing	0.003	N	0.159	neutral	None	None	None	None	N
E/T	0.1508	likely_benign	0.1347	benign	-0.742	Destabilizing	0.001	N	0.219	neutral	None	None	None	None	N
E/V	0.1466	likely_benign	0.1286	benign	-0.135	Destabilizing	None	N	0.231	neutral	N	0.509815767	None	None	N
E/W	0.7971	likely_pathogenic	0.7535	pathogenic	0.236	Stabilizing	0.864	D	0.261	neutral	None	None	None	None	N
E/Y	0.4478	ambiguous	0.397	ambiguous	0.189	Stabilizing	0.356	N	0.299	neutral	None	None	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.