TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13925	41998;41999;42000	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
N2AB	12284	37075;37076;37077	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
N2A	11357	34294;34295;34296	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
N2B	4860	14803;14804;14805	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
Novex-1	4985	15178;15179;15180	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
Novex-2	5052	15379;15380;15381	chr2:178635551;178635550;178635549	chr2:179500278;179500277;179500276
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-89
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.4601
• 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
R/G	None	None	0.058	N	0.451	0.186	0.335414705075	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/T	None	None	0.058	N	0.447	0.065	0.229264304666	gnomAD-4.0.0	6.92981E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.67493E-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
R/A	0.6135	likely_pathogenic	0.6495	pathogenic	-0.25	Destabilizing	0.016	N	0.391	neutral	None	None	None	None	N
R/C	0.3417	ambiguous	0.3476	ambiguous	-0.378	Destabilizing	0.869	D	0.411	neutral	None	None	None	None	N
R/D	0.8831	likely_pathogenic	0.893	pathogenic	-0.014	Destabilizing	0.075	N	0.389	neutral	None	None	None	None	N
R/E	0.5506	ambiguous	0.5408	ambiguous	0.086	Stabilizing	0.016	N	0.357	neutral	None	None	None	None	N
R/F	0.7023	likely_pathogenic	0.7262	pathogenic	-0.344	Destabilizing	0.637	D	0.489	neutral	None	None	None	None	N
R/G	0.5238	ambiguous	0.5691	pathogenic	-0.498	Destabilizing	0.058	N	0.451	neutral	N	0.441698189	None	None	N
R/H	0.1421	likely_benign	0.139	benign	-1.01	Destabilizing	0.366	N	0.375	neutral	None	None	None	None	N
R/I	0.4598	ambiguous	0.4468	ambiguous	0.386	Stabilizing	0.303	N	0.546	neutral	N	0.401905369	None	None	N
R/K	0.0708	likely_benign	0.0712	benign	-0.236	Destabilizing	None	N	0.111	neutral	N	0.322757743	None	None	N
R/L	0.3936	ambiguous	0.409	ambiguous	0.386	Stabilizing	0.075	N	0.451	neutral	None	None	None	None	N
R/M	0.4093	ambiguous	0.4214	ambiguous	-0.078	Destabilizing	0.637	D	0.415	neutral	None	None	None	None	N
R/N	0.7645	likely_pathogenic	0.7789	pathogenic	-0.005	Destabilizing	0.075	N	0.333	neutral	None	None	None	None	N
R/P	0.8622	likely_pathogenic	0.9094	pathogenic	0.196	Stabilizing	0.141	N	0.45	neutral	None	None	None	None	N
R/Q	0.1475	likely_benign	0.1397	benign	-0.087	Destabilizing	0.039	N	0.371	neutral	None	None	None	None	N
R/S	0.7039	likely_pathogenic	0.7208	pathogenic	-0.506	Destabilizing	0.012	N	0.413	neutral	N	0.420925081	None	None	N
R/T	0.4225	ambiguous	0.4186	ambiguous	-0.24	Destabilizing	0.058	N	0.447	neutral	N	0.441515675	None	None	N
R/V	0.5167	ambiguous	0.526	ambiguous	0.196	Stabilizing	0.075	N	0.514	neutral	None	None	None	None	N
R/W	0.2831	likely_benign	0.2768	benign	-0.277	Destabilizing	0.869	D	0.443	neutral	None	None	None	None	N
R/Y	0.5747	likely_pathogenic	0.5853	pathogenic	0.11	Stabilizing	0.637	D	0.505	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.