TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1605	5038;5039;5040	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
N2AB	1605	5038;5039;5040	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
N2A	1605	5038;5039;5040	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
N2B	1559	4900;4901;4902	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
Novex-1	1559	4900;4901;4902	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
Novex-2	1559	4900;4901;4902	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776
Novex-3	1605	5038;5039;5040	chr2:178777150;178777149;178777049	chr2:179641877;179641876;179641776

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-7
• Domain position: 50
• Structural Position: 122
• Q(SASA): 0.4041
• 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	0.324	N	0.507	0.29	0.490839437361	gnomAD-4.0.0	6.8411E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99332E-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
R/A	0.3529	ambiguous	0.3186	benign	-0.327	Destabilizing	0.116	N	0.428	neutral	None	None	None	None	N
R/C	0.1893	likely_benign	0.1702	benign	-0.281	Destabilizing	0.981	D	0.536	neutral	None	None	None	None	N
R/D	0.7276	likely_pathogenic	0.6674	pathogenic	0.066	Stabilizing	0.388	N	0.547	neutral	None	None	None	None	N
R/E	0.3798	ambiguous	0.3275	benign	0.181	Stabilizing	0.116	N	0.408	neutral	None	None	None	None	N
R/F	0.4955	ambiguous	0.4538	ambiguous	-0.205	Destabilizing	0.69	D	0.563	neutral	None	None	None	None	N
R/G	0.3005	likely_benign	0.2646	benign	-0.626	Destabilizing	0.324	N	0.507	neutral	N	0.50832044	None	None	N
R/H	0.1014	likely_benign	0.0975	benign	-1.074	Destabilizing	0.818	D	0.483	neutral	None	None	None	None	N
R/I	0.2012	likely_benign	0.1894	benign	0.459	Stabilizing	0.001	N	0.36	neutral	N	0.513550498	None	None	N
R/K	0.0859	likely_benign	0.0851	benign	-0.391	Destabilizing	None	N	0.109	neutral	N	0.459842192	None	None	N
R/L	0.2389	likely_benign	0.2216	benign	0.459	Stabilizing	0.116	N	0.434	neutral	None	None	None	None	N
R/M	0.2221	likely_benign	0.2022	benign	0.026	Stabilizing	0.69	D	0.529	neutral	None	None	None	None	N
R/N	0.5102	ambiguous	0.4685	ambiguous	0.076	Stabilizing	0.388	N	0.455	neutral	None	None	None	None	N
R/P	0.9389	likely_pathogenic	0.9113	pathogenic	0.219	Stabilizing	0.818	D	0.543	neutral	None	None	None	None	N
R/Q	0.1014	likely_benign	0.0964	benign	-0.038	Destabilizing	0.241	N	0.468	neutral	None	None	None	None	N
R/S	0.4068	ambiguous	0.3701	ambiguous	-0.507	Destabilizing	0.193	N	0.471	neutral	N	0.481867867	None	None	N
R/T	0.1937	likely_benign	0.1751	benign	-0.218	Destabilizing	0.324	N	0.481	neutral	N	0.496188431	None	None	N
R/V	0.2691	likely_benign	0.2465	benign	0.219	Stabilizing	0.098	N	0.499	neutral	None	None	None	None	N
R/W	0.2036	likely_benign	0.1819	benign	0.003	Stabilizing	0.981	D	0.577	neutral	None	None	None	None	N
R/Y	0.4117	ambiguous	0.3746	ambiguous	0.332	Stabilizing	0.818	D	0.561	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.