TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30874	92845;92846;92847	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
N2AB	29233	87922;87923;87924	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
N2A	28306	85141;85142;85143	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
N2B	21809	65650;65651;65652	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
Novex-1	21934	66025;66026;66027	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
Novex-2	22001	66226;66227;66228	chr2:178549006;178549005;178549004	chr2:179413733;179413732;179413731
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-113
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.9188
• 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/K	None	None	0.565	N	0.429	0.249	0.208816687407	gnomAD-4.0.0	1.59108E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02371E-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	0.1326	likely_benign	0.1311	benign	0.016	Stabilizing	0.349	N	0.465	neutral	N	0.394709803	None	None	I
E/C	0.8188	likely_pathogenic	0.8277	pathogenic	-0.05	Destabilizing	0.996	D	0.551	neutral	None	None	None	None	I
E/D	0.1034	likely_benign	0.1037	benign	-0.283	Destabilizing	0.517	D	0.381	neutral	N	0.425992715	None	None	I
E/F	0.7055	likely_pathogenic	0.7184	pathogenic	-0.133	Destabilizing	0.987	D	0.494	neutral	None	None	None	None	I
E/G	0.1701	likely_benign	0.1684	benign	-0.078	Destabilizing	0.722	D	0.493	neutral	N	0.407273668	None	None	I
E/H	0.4057	ambiguous	0.4126	ambiguous	0.428	Stabilizing	0.961	D	0.392	neutral	None	None	None	None	I
E/I	0.3357	likely_benign	0.3363	benign	0.198	Stabilizing	0.961	D	0.493	neutral	None	None	None	None	I
E/K	0.1402	likely_benign	0.1337	benign	0.452	Stabilizing	0.565	D	0.429	neutral	N	0.402193136	None	None	I
E/L	0.3755	ambiguous	0.3775	ambiguous	0.198	Stabilizing	0.775	D	0.465	neutral	None	None	None	None	I
E/M	0.4274	ambiguous	0.4306	ambiguous	0.05	Stabilizing	0.996	D	0.475	neutral	None	None	None	None	I
E/N	0.2193	likely_benign	0.2173	benign	0.339	Stabilizing	0.875	D	0.399	neutral	None	None	None	None	I
E/P	0.6084	likely_pathogenic	0.5944	pathogenic	0.155	Stabilizing	0.011	N	0.271	neutral	None	None	None	None	I
E/Q	0.1364	likely_benign	0.1381	benign	0.323	Stabilizing	0.092	N	0.167	neutral	N	0.417933379	None	None	I
E/R	0.2407	likely_benign	0.2362	benign	0.612	Stabilizing	0.775	D	0.407	neutral	None	None	None	None	I
E/S	0.175	likely_benign	0.173	benign	0.179	Stabilizing	0.775	D	0.416	neutral	None	None	None	None	I
E/T	0.1743	likely_benign	0.1755	benign	0.259	Stabilizing	0.775	D	0.475	neutral	None	None	None	None	I
E/V	0.1858	likely_benign	0.1856	benign	0.155	Stabilizing	0.722	D	0.442	neutral	N	0.405118798	None	None	I
E/W	0.8895	likely_pathogenic	0.8947	pathogenic	-0.126	Destabilizing	0.996	D	0.579	neutral	None	None	None	None	I
E/Y	0.5951	likely_pathogenic	0.5966	pathogenic	0.083	Stabilizing	0.987	D	0.471	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.