TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23270	70033;70034;70035	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
N2AB	21629	65110;65111;65112	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
N2A	20702	62329;62330;62331	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
N2B	14205	42838;42839;42840	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
Novex-1	14330	43213;43214;43215	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
Novex-2	14397	43414;43415;43416	chr2:178576324;178576323;178576322	chr2:179441051;179441050;179441049
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-57
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.3805
• 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
L/F	rs904477168	None	0.994	N	0.785	0.163	0.596456784696	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs904477168	None	0.994	N	0.785	0.163	0.596456784696	gnomAD-4.0.0	6.57523E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4708E-05	0	0
L/I	None	None	0.979	N	0.617	0.173	0.508934680445	gnomAD-4.0.0	2.82019E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.65396E-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
L/A	0.2469	likely_benign	0.2452	benign	-1.109	Destabilizing	0.938	D	0.553	neutral	None	None	None	None	I
L/C	0.4146	ambiguous	0.4121	ambiguous	-0.64	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
L/D	0.7943	likely_pathogenic	0.7873	pathogenic	-0.527	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	I
L/E	0.4503	ambiguous	0.4652	ambiguous	-0.609	Destabilizing	0.991	D	0.804	deleterious	None	None	None	None	I
L/F	0.2255	likely_benign	0.22	benign	-1.076	Destabilizing	0.994	D	0.785	deleterious	N	0.466836108	None	None	I
L/G	0.4808	ambiguous	0.4711	ambiguous	-1.324	Destabilizing	0.982	D	0.787	deleterious	None	None	None	None	I
L/H	0.3226	likely_benign	0.3159	benign	-0.587	Destabilizing	0.999	D	0.839	deleterious	N	0.493025784	None	None	I
L/I	0.2485	likely_benign	0.2588	benign	-0.645	Destabilizing	0.979	D	0.617	neutral	N	0.496546092	None	None	I
L/K	0.2591	likely_benign	0.2541	benign	-0.522	Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	I
L/M	0.1005	likely_benign	0.1073	benign	-0.387	Destabilizing	0.998	D	0.764	deleterious	None	None	None	None	I
L/N	0.4696	ambiguous	0.4722	ambiguous	-0.23	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	I
L/P	0.9492	likely_pathogenic	0.9465	pathogenic	-0.766	Destabilizing	0.994	D	0.826	deleterious	N	0.515651927	None	None	I
L/Q	0.1578	likely_benign	0.1587	benign	-0.523	Destabilizing	0.991	D	0.836	deleterious	None	None	None	None	I
L/R	0.217	likely_benign	0.203	benign	0.099	Stabilizing	0.988	D	0.826	deleterious	N	0.465529751	None	None	I
L/S	0.253	likely_benign	0.2511	benign	-0.766	Destabilizing	0.484	N	0.591	neutral	None	None	None	None	I
L/T	0.2947	likely_benign	0.293	benign	-0.739	Destabilizing	0.938	D	0.721	prob.delet.	None	None	None	None	I
L/V	0.1784	likely_benign	0.1837	benign	-0.766	Destabilizing	0.958	D	0.612	neutral	N	0.485251663	None	None	I
L/W	0.4136	ambiguous	0.3987	ambiguous	-1.056	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
L/Y	0.4423	ambiguous	0.4313	ambiguous	-0.805	Destabilizing	0.998	D	0.761	deleterious	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.