TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2668	8227;8228;8229	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
N2AB	2668	8227;8228;8229	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
N2A	2668	8227;8228;8229	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
N2B	2622	8089;8090;8091	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
Novex-1	2622	8089;8090;8091	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
Novex-2	2622	8089;8090;8091	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050
Novex-3	2668	8227;8228;8229	chr2:178771325;178771324;178771323	chr2:179636052;179636051;179636050

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-16
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.3519
• 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/Q	rs766594353	-0.149	0.075	N	0.207	0.188	0.193865811164	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
E/Q	rs766594353	-0.149	0.075	N	0.207	0.188	0.193865811164	gnomAD-4.0.0	2.05226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7986E-06	1.15931E-05	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	0.1739	likely_benign	0.1778	benign	-0.732	Destabilizing	0.565	D	0.501	neutral	N	0.505749689	None	None	N
E/C	0.8495	likely_pathogenic	0.8486	pathogenic	-0.274	Destabilizing	0.996	D	0.708	prob.delet.	None	None	None	None	N
E/D	0.193	likely_benign	0.2005	benign	-0.996	Destabilizing	0.008	N	0.21	neutral	N	0.505749689	None	None	N
E/F	0.6131	likely_pathogenic	0.6237	pathogenic	-0.469	Destabilizing	0.987	D	0.699	prob.neutral	None	None	None	None	N
E/G	0.2431	likely_benign	0.2337	benign	-1.036	Destabilizing	0.722	D	0.597	neutral	N	0.506735657	None	None	N
E/H	0.4226	ambiguous	0.408	ambiguous	-0.647	Destabilizing	0.961	D	0.53	neutral	None	None	None	None	N
E/I	0.2262	likely_benign	0.2358	benign	0.074	Stabilizing	0.961	D	0.715	prob.delet.	None	None	None	None	N
E/K	0.1377	likely_benign	0.1291	benign	-0.259	Destabilizing	0.008	N	0.223	neutral	N	0.506598944	None	None	N
E/L	0.3645	ambiguous	0.3613	ambiguous	0.074	Stabilizing	0.923	D	0.654	neutral	None	None	None	None	N
E/M	0.4003	ambiguous	0.3958	ambiguous	0.45	Stabilizing	0.989	D	0.681	prob.neutral	None	None	None	None	N
E/N	0.3168	likely_benign	0.3313	benign	-0.657	Destabilizing	0.775	D	0.484	neutral	None	None	None	None	N
E/P	0.9451	likely_pathogenic	0.9269	pathogenic	-0.173	Destabilizing	0.961	D	0.604	neutral	None	None	None	None	N
E/Q	0.1427	likely_benign	0.1358	benign	-0.594	Destabilizing	0.075	N	0.207	neutral	N	0.509677242	None	None	N
E/R	0.2687	likely_benign	0.245	benign	-0.053	Destabilizing	0.633	D	0.484	neutral	None	None	None	None	N
E/S	0.2307	likely_benign	0.2405	benign	-0.899	Destabilizing	0.633	D	0.458	neutral	None	None	None	None	N
E/T	0.2126	likely_benign	0.2165	benign	-0.653	Destabilizing	0.923	D	0.539	neutral	None	None	None	None	N
E/V	0.1505	likely_benign	0.1505	benign	-0.173	Destabilizing	0.901	D	0.623	neutral	N	0.505396097	None	None	N
E/W	0.8872	likely_pathogenic	0.8813	pathogenic	-0.269	Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
E/Y	0.561	ambiguous	0.5639	ambiguous	-0.214	Destabilizing	0.961	D	0.689	prob.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.