TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17414	52465;52466;52467	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
N2AB	15773	47542;47543;47544	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
N2A	14846	44761;44762;44763	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
N2B	8349	25270;25271;25272	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
Novex-1	8474	25645;25646;25647	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
Novex-2	8541	25846;25847;25848	chr2:178608771;178608770;178608769	chr2:179473498;179473497;179473496
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-14
• Domain position: 46
• Structural Position: 61
• Q(SASA): 0.3442
• 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
P/L	rs2154197858	None	None	N	0.155	0.248	0.395441342475	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs2154197858	None	None	N	0.155	0.248	0.395441342475	gnomAD-4.0.0	6.57791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47275E-05	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
P/A	0.0682	likely_benign	0.0702	benign	-0.207	Destabilizing	None	N	0.153	neutral	N	0.40952454	None	None	N
P/C	0.453	ambiguous	0.4297	ambiguous	-0.61	Destabilizing	0.667	D	0.363	neutral	None	None	None	None	N
P/D	0.2584	likely_benign	0.2692	benign	-0.107	Destabilizing	0.22	N	0.301	neutral	None	None	None	None	N
P/E	0.1817	likely_benign	0.1901	benign	-0.234	Destabilizing	0.055	N	0.311	neutral	None	None	None	None	N
P/F	0.4515	ambiguous	0.4262	ambiguous	-0.628	Destabilizing	0.22	N	0.44	neutral	None	None	None	None	N
P/G	0.2107	likely_benign	0.2022	benign	-0.274	Destabilizing	0.055	N	0.264	neutral	None	None	None	None	N
P/H	0.1898	likely_benign	0.1864	benign	0.032	Stabilizing	0.602	D	0.335	neutral	N	0.468303485	None	None	N
P/I	0.212	likely_benign	0.2131	benign	-0.188	Destabilizing	0.055	N	0.257	neutral	None	None	None	None	N
P/K	0.2196	likely_benign	0.2189	benign	-0.179	Destabilizing	0.055	N	0.322	neutral	None	None	None	None	N
P/L	0.1103	likely_benign	0.1078	benign	-0.188	Destabilizing	None	N	0.155	neutral	N	0.42101097	None	None	N
P/M	0.2015	likely_benign	0.1971	benign	-0.311	Destabilizing	0.497	N	0.365	neutral	None	None	None	None	N
P/N	0.1988	likely_benign	0.2051	benign	0.048	Stabilizing	0.124	N	0.305	neutral	None	None	None	None	N
P/Q	0.1346	likely_benign	0.1348	benign	-0.181	Destabilizing	0.22	N	0.295	neutral	None	None	None	None	N
P/R	0.204	likely_benign	0.1946	benign	0.247	Stabilizing	0.001	N	0.199	neutral	N	0.432940117	None	None	N
P/S	0.1045	likely_benign	0.1051	benign	-0.277	Destabilizing	None	N	0.14	neutral	N	0.414487642	None	None	N
P/T	0.0787	likely_benign	0.0815	benign	-0.308	Destabilizing	0.042	N	0.333	neutral	N	0.427590226	None	None	N
P/V	0.1464	likely_benign	0.1447	benign	-0.164	Destabilizing	0.002	N	0.155	neutral	None	None	None	None	N
P/W	0.5835	likely_pathogenic	0.55	ambiguous	-0.705	Destabilizing	0.958	D	0.368	neutral	None	None	None	None	N
P/Y	0.39	ambiguous	0.3827	ambiguous	-0.39	Destabilizing	0.667	D	0.437	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.