TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4618	14077;14078;14079	chr2:178739381;178739380;178739379	chr2:179604108;179604107;179604106
N2AB	4301	13126;13127;13128	chr2:178739381;178739380;178739379	chr2:179604108;179604107;179604106
N2A	None	None	chr2:None	chr2:None
N2B	4255	12988;12989;12990	chr2:178739381;178739380;178739379	chr2:179604108;179604107;179604106
Novex-1	4380	13363;13364;13365	chr2:178739381;178739380;178739379	chr2:179604108;179604107;179604106
Novex-2	4447	13564;13565;13566	chr2:178739381;178739380;178739379	chr2:179604108;179604107;179604106
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-29
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.6181
• 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/G	rs774836172	-0.657	0.722	D	0.625	0.378	0.357313475932	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/G	rs774836172	-0.657	0.722	D	0.625	0.378	0.357313475932	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/G	rs774836172	-0.657	0.722	D	0.625	0.378	0.357313475932	gnomAD-4.0.0	1.67309E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.11894E-05	0	3.20195E-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
E/A	0.1544	likely_benign	0.1559	benign	-0.372	Destabilizing	0.565	D	0.58	neutral	N	0.504632284	None	None	N
E/C	0.7921	likely_pathogenic	0.8096	pathogenic	-0.02	Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.1895	likely_benign	0.206	benign	-0.355	Destabilizing	0.008	N	0.297	neutral	N	0.512652949	None	None	N
E/F	0.668	likely_pathogenic	0.6795	pathogenic	-0.27	Destabilizing	0.987	D	0.656	neutral	None	None	None	None	N
E/G	0.1527	likely_benign	0.1672	benign	-0.554	Destabilizing	0.722	D	0.625	neutral	D	0.600480297	None	None	N
E/H	0.4298	ambiguous	0.4734	ambiguous	0.014	Stabilizing	0.989	D	0.503	neutral	None	None	None	None	N
E/I	0.338	likely_benign	0.3432	ambiguous	0.07	Stabilizing	0.961	D	0.661	neutral	None	None	None	None	N
E/K	0.0836	likely_benign	0.1013	benign	0.421	Stabilizing	0.008	N	0.318	neutral	N	0.507936956	None	None	N
E/L	0.32	likely_benign	0.3441	ambiguous	0.07	Stabilizing	0.923	D	0.631	neutral	None	None	None	None	N
E/M	0.3685	ambiguous	0.3894	ambiguous	0.158	Stabilizing	0.996	D	0.663	neutral	None	None	None	None	N
E/N	0.2679	likely_benign	0.3032	benign	0.033	Stabilizing	0.923	D	0.491	neutral	None	None	None	None	N
E/P	0.4972	ambiguous	0.5242	ambiguous	-0.058	Destabilizing	0.024	N	0.369	neutral	None	None	None	None	N
E/Q	0.1318	likely_benign	0.1416	benign	0.068	Stabilizing	0.565	D	0.497	neutral	N	0.501023868	None	None	N
E/R	0.1518	likely_benign	0.1769	benign	0.597	Stabilizing	0.858	D	0.487	neutral	None	None	None	None	N
E/S	0.2088	likely_benign	0.2213	benign	-0.092	Destabilizing	0.633	D	0.512	neutral	None	None	None	None	N
E/T	0.2218	likely_benign	0.2366	benign	0.063	Stabilizing	0.775	D	0.564	neutral	None	None	None	None	N
E/V	0.1942	likely_benign	0.1952	benign	-0.058	Destabilizing	0.901	D	0.604	neutral	N	0.512609915	None	None	N
E/W	0.8431	likely_pathogenic	0.8686	pathogenic	-0.12	Destabilizing	0.996	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.5756	likely_pathogenic	0.6059	pathogenic	-0.024	Destabilizing	0.987	D	0.646	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.