TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26002	78229;78230;78231	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
N2AB	24361	73306;73307;73308	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
N2A	23434	70525;70526;70527	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
N2B	16937	51034;51035;51036	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
Novex-1	17062	51409;51410;51411	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
Novex-2	17129	51610;51611;51612	chr2:178568128;178568127;178568126	chr2:179432855;179432854;179432853
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-77
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2268
• 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
I/M	None	None	0.171	N	0.343	0.111	0.344945010812	gnomAD-4.0.0	2.05303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69876E-06	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
I/A	0.1684	likely_benign	0.2077	benign	-1.698	Destabilizing	0.007	N	0.274	neutral	None	None	None	None	N
I/C	0.4416	ambiguous	0.4646	ambiguous	-1.208	Destabilizing	0.356	N	0.331	neutral	None	None	None	None	N
I/D	0.6418	likely_pathogenic	0.7277	pathogenic	-1.21	Destabilizing	0.072	N	0.478	neutral	None	None	None	None	N
I/E	0.5602	ambiguous	0.6369	pathogenic	-1.211	Destabilizing	0.072	N	0.451	neutral	None	None	None	None	N
I/F	0.1308	likely_benign	0.1495	benign	-1.472	Destabilizing	None	N	0.099	neutral	N	0.508614099	None	None	N
I/G	0.4346	ambiguous	0.5236	ambiguous	-2.008	Highly Destabilizing	0.072	N	0.39	neutral	None	None	None	None	N
I/H	0.4394	ambiguous	0.5139	ambiguous	-1.365	Destabilizing	0.214	N	0.449	neutral	None	None	None	None	N
I/K	0.3764	ambiguous	0.4473	ambiguous	-0.966	Destabilizing	0.072	N	0.453	neutral	None	None	None	None	N
I/L	0.1016	likely_benign	0.1015	benign	-0.919	Destabilizing	0.002	N	0.231	neutral	N	0.462262947	None	None	N
I/M	0.1056	likely_benign	0.1108	benign	-0.725	Destabilizing	0.171	N	0.343	neutral	N	0.47286695	None	None	N
I/N	0.212	likely_benign	0.2813	benign	-0.807	Destabilizing	0.055	N	0.521	neutral	N	0.48362737	None	None	N
I/P	0.5078	ambiguous	0.5769	pathogenic	-1.149	Destabilizing	0.356	N	0.521	neutral	None	None	None	None	N
I/Q	0.3919	ambiguous	0.458	ambiguous	-1.021	Destabilizing	0.356	N	0.501	neutral	None	None	None	None	N
I/R	0.2929	likely_benign	0.356	ambiguous	-0.455	Destabilizing	0.356	N	0.509	neutral	None	None	None	None	N
I/S	0.1736	likely_benign	0.2237	benign	-1.449	Destabilizing	0.012	N	0.358	neutral	N	0.478117833	None	None	N
I/T	0.1387	likely_benign	0.1742	benign	-1.331	Destabilizing	None	N	0.146	neutral	N	0.475808247	None	None	N
I/V	0.0581	likely_benign	0.0574	benign	-1.149	Destabilizing	None	N	0.073	neutral	N	0.395824524	None	None	N
I/W	0.767	likely_pathogenic	0.7937	pathogenic	-1.536	Destabilizing	0.628	D	0.415	neutral	None	None	None	None	N
I/Y	0.4349	ambiguous	0.4873	ambiguous	-1.257	Destabilizing	None	N	0.113	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.