TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9272	28039;28040;28041	chr2:178712016;178712015;178712014	chr2:179576743;179576742;179576741
N2AB	8955	27088;27089;27090	chr2:178712016;178712015;178712014	chr2:179576743;179576742;179576741
N2A	8028	24307;24308;24309	chr2:178712016;178712015;178712014	chr2:179576743;179576742;179576741
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-78
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2081
• 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
S/R	None	None	0.001	N	0.299	0.3	0.250039746154	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	0	0
S/T	rs763783812	-0.565	0.081	N	0.427	0.116	0.180583059064	gnomAD-2.1.1	2.81E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96309E-04	None	0	8.87E-06	0
S/T	rs763783812	-0.565	0.081	N	0.427	0.116	0.180583059064	gnomAD-4.0.0	1.43693E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59809E-06	1.97179E-04	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
S/A	0.0778	likely_benign	0.0798	benign	-0.751	Destabilizing	0.025	N	0.361	neutral	None	None	None	None	N
S/C	0.146	likely_benign	0.1614	benign	-0.469	Destabilizing	0.946	D	0.493	neutral	D	0.531085687	None	None	N
S/D	0.4493	ambiguous	0.4763	ambiguous	0.079	Stabilizing	0.22	N	0.437	neutral	None	None	None	None	N
S/E	0.5204	ambiguous	0.5148	ambiguous	0.053	Stabilizing	0.22	N	0.438	neutral	None	None	None	None	N
S/F	0.2512	likely_benign	0.3008	benign	-1.013	Destabilizing	0.667	D	0.542	neutral	None	None	None	None	N
S/G	0.0931	likely_benign	0.1097	benign	-0.969	Destabilizing	None	N	0.137	neutral	N	0.486697196	None	None	N
S/H	0.3868	ambiguous	0.4163	ambiguous	-1.418	Destabilizing	0.859	D	0.513	neutral	None	None	None	None	N
S/I	0.1503	likely_benign	0.1629	benign	-0.284	Destabilizing	0.001	N	0.293	neutral	N	0.494370198	None	None	N
S/K	0.5537	ambiguous	0.5669	pathogenic	-0.587	Destabilizing	0.124	N	0.43	neutral	None	None	None	None	N
S/L	0.1104	likely_benign	0.1267	benign	-0.284	Destabilizing	0.055	N	0.391	neutral	None	None	None	None	N
S/M	0.1967	likely_benign	0.21	benign	0.013	Stabilizing	0.667	D	0.527	neutral	None	None	None	None	N
S/N	0.1582	likely_benign	0.1777	benign	-0.456	Destabilizing	0.175	N	0.441	neutral	N	0.502079199	None	None	N
S/P	0.6159	likely_pathogenic	0.6718	pathogenic	-0.407	Destabilizing	0.667	D	0.539	neutral	None	None	None	None	N
S/Q	0.4814	ambiguous	0.4868	ambiguous	-0.651	Destabilizing	0.497	N	0.505	neutral	None	None	None	None	N
S/R	0.42	ambiguous	0.4646	ambiguous	-0.461	Destabilizing	0.001	N	0.299	neutral	N	0.500104189	None	None	N
S/T	0.079	likely_benign	0.0827	benign	-0.563	Destabilizing	0.081	N	0.427	neutral	N	0.503411428	None	None	N
S/V	0.1842	likely_benign	0.1929	benign	-0.407	Destabilizing	0.004	N	0.301	neutral	None	None	None	None	N
S/W	0.4325	ambiguous	0.516	ambiguous	-0.941	Destabilizing	0.958	D	0.581	neutral	None	None	None	None	N
S/Y	0.2468	likely_benign	0.2792	benign	-0.691	Destabilizing	0.859	D	0.539	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.