TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30803	92632;92633;92634	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
N2AB	29162	87709;87710;87711	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
N2A	28235	84928;84929;84930	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
N2B	21738	65437;65438;65439	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
Novex-1	21863	65812;65813;65814	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
Novex-2	21930	66013;66014;66015	chr2:178549219;178549218;178549217	chr2:179413946;179413945;179413944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-112
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3382
• 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
V/A	None	None	0.104	N	0.513	0.201	0.419335720491	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
V/A	0.1236	likely_benign	0.126	benign	-1.349	Destabilizing	0.104	N	0.513	neutral	N	0.508395094	None	None	N
V/C	0.5761	likely_pathogenic	0.6019	pathogenic	-0.824	Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	N
V/D	0.4506	ambiguous	0.4565	ambiguous	-1.284	Destabilizing	0.667	D	0.795	deleterious	N	0.465818468	None	None	N
V/E	0.3257	likely_benign	0.3406	ambiguous	-1.344	Destabilizing	0.726	D	0.785	deleterious	None	None	None	None	N
V/F	0.1542	likely_benign	0.1508	benign	-1.228	Destabilizing	0.497	N	0.715	prob.delet.	N	0.482171285	None	None	N
V/G	0.2595	likely_benign	0.2563	benign	-1.598	Destabilizing	0.667	D	0.777	deleterious	N	0.47654289	None	None	N
V/H	0.5274	ambiguous	0.5295	ambiguous	-1.071	Destabilizing	0.968	D	0.796	deleterious	None	None	None	None	N
V/I	0.0604	likely_benign	0.0603	benign	-0.791	Destabilizing	None	N	0.221	neutral	N	0.455062041	None	None	N
V/K	0.3261	likely_benign	0.3357	benign	-1.088	Destabilizing	0.726	D	0.784	deleterious	None	None	None	None	N
V/L	0.1376	likely_benign	0.1402	benign	-0.791	Destabilizing	None	N	0.257	neutral	N	0.443863613	None	None	N
V/M	0.1174	likely_benign	0.116	benign	-0.519	Destabilizing	0.567	D	0.659	neutral	None	None	None	None	N
V/N	0.2626	likely_benign	0.2697	benign	-0.797	Destabilizing	0.89	D	0.799	deleterious	None	None	None	None	N
V/P	0.3055	likely_benign	0.3407	ambiguous	-0.942	Destabilizing	0.89	D	0.787	deleterious	None	None	None	None	N
V/Q	0.3114	likely_benign	0.3228	benign	-1.075	Destabilizing	0.89	D	0.791	deleterious	None	None	None	None	N
V/R	0.2656	likely_benign	0.2711	benign	-0.437	Destabilizing	0.726	D	0.797	deleterious	None	None	None	None	N
V/S	0.1971	likely_benign	0.1982	benign	-1.23	Destabilizing	0.726	D	0.759	deleterious	None	None	None	None	N
V/T	0.1098	likely_benign	0.1174	benign	-1.194	Destabilizing	0.272	N	0.593	neutral	None	None	None	None	N
V/W	0.7089	likely_pathogenic	0.7021	pathogenic	-1.331	Destabilizing	0.968	D	0.793	deleterious	None	None	None	None	N
V/Y	0.4613	ambiguous	0.4673	ambiguous	-1.073	Destabilizing	0.726	D	0.71	prob.delet.	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.