TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4825	14698;14699;14700	chr2:178735973;178735972;178735971	chr2:179600700;179600699;179600698
N2AB	4508	13747;13748;13749	chr2:178735973;178735972;178735971	chr2:179600700;179600699;179600698
N2A	3581	10966;10967;10968	chr2:178735973;178735972;178735971	chr2:179600700;179600699;179600698
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-31
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.6382
• Predicted PPI site: I

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/A	rs769228664	-0.262	0.006	N	0.241	0.246	0.353548585375	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/A	rs769228664	-0.262	0.006	N	0.241	0.246	0.353548585375	gnomAD-4.0.0	6.8421E-07	None	None	None	None	I	None	0	2.23624E-05	None	0	0	None	0	0	0	0	0
E/V	None	None	0.324	N	0.55	0.303	0.556811950826	gnomAD-4.0.0	2.05263E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31873E-05	1.65656E-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
E/A	0.2651	likely_benign	0.219	benign	-0.307	Destabilizing	0.006	N	0.241	neutral	N	0.512456368	None	None	I
E/C	0.9258	likely_pathogenic	0.882	pathogenic	-0.022	Destabilizing	0.981	D	0.509	neutral	None	None	None	None	I
E/D	0.1452	likely_benign	0.1241	benign	-0.364	Destabilizing	None	N	0.107	neutral	N	0.478171916	None	None	I
E/F	0.8816	likely_pathogenic	0.8348	pathogenic	-0.172	Destabilizing	0.932	D	0.525	neutral	None	None	None	None	I
E/G	0.274	likely_benign	0.2131	benign	-0.504	Destabilizing	0.165	N	0.455	neutral	D	0.566482757	None	None	I
E/H	0.5123	ambiguous	0.4199	ambiguous	0.056	Stabilizing	0.818	D	0.487	neutral	None	None	None	None	I
E/I	0.6435	likely_pathogenic	0.5536	ambiguous	0.176	Stabilizing	0.818	D	0.549	neutral	None	None	None	None	I
E/K	0.1904	likely_benign	0.1403	benign	0.422	Stabilizing	0.324	N	0.442	neutral	N	0.398710167	None	None	I
E/L	0.6312	likely_pathogenic	0.5527	ambiguous	0.176	Stabilizing	0.388	N	0.556	neutral	None	None	None	None	I
E/M	0.6867	likely_pathogenic	0.5981	pathogenic	0.215	Stabilizing	0.981	D	0.504	neutral	None	None	None	None	I
E/N	0.3047	likely_benign	0.2443	benign	0.036	Stabilizing	0.004	N	0.123	neutral	None	None	None	None	I
E/P	0.9116	likely_pathogenic	0.8251	pathogenic	0.035	Stabilizing	0.818	D	0.551	neutral	None	None	None	None	I
E/Q	0.1705	likely_benign	0.1353	benign	0.08	Stabilizing	0.324	N	0.47	neutral	N	0.49834967	None	None	I
E/R	0.3296	likely_benign	0.2472	benign	0.596	Stabilizing	0.388	N	0.492	neutral	None	None	None	None	I
E/S	0.2679	likely_benign	0.2173	benign	-0.09	Destabilizing	0.116	N	0.444	neutral	None	None	None	None	I
E/T	0.3082	likely_benign	0.2461	benign	0.075	Stabilizing	0.388	N	0.501	neutral	None	None	None	None	I
E/V	0.4143	ambiguous	0.3351	benign	0.035	Stabilizing	0.324	N	0.55	neutral	N	0.507135149	None	None	I
E/W	0.9507	likely_pathogenic	0.9177	pathogenic	-0.025	Destabilizing	0.981	D	0.593	neutral	None	None	None	None	I
E/Y	0.7553	likely_pathogenic	0.6777	pathogenic	0.075	Stabilizing	0.932	D	0.526	neutral	None	None	None	None	I

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.