TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32959	99100;99101;99102	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
N2AB	31318	94177;94178;94179	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
N2A	30391	91396;91397;91398	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
N2B	23894	71905;71906;71907	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
Novex-1	24019	72280;72281;72282	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
Novex-2	24086	72481;72482;72483	chr2:178539060;178539059;178539058	chr2:179403787;179403786;179403785
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-128
• Domain position: 64
• Structural Position: 93
• Q(SASA): 0.0902
• 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/L	None	None	0.003	N	0.289	0.122	0.336400405673	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
V/A	0.7809	likely_pathogenic	0.7516	pathogenic	-1.787	Destabilizing	0.722	D	0.659	neutral	N	0.475201262	None	None	N
V/C	0.957	likely_pathogenic	0.9487	pathogenic	-1.548	Destabilizing	0.996	D	0.756	deleterious	None	None	None	None	N
V/D	0.9955	likely_pathogenic	0.9939	pathogenic	-2.325	Highly Destabilizing	0.983	D	0.817	deleterious	N	0.491988844	None	None	N
V/E	0.9826	likely_pathogenic	0.9769	pathogenic	-2.035	Highly Destabilizing	0.987	D	0.802	deleterious	None	None	None	None	N
V/F	0.7862	likely_pathogenic	0.7666	pathogenic	-1.076	Destabilizing	0.901	D	0.779	deleterious	N	0.503594958	None	None	N
V/G	0.9586	likely_pathogenic	0.9478	pathogenic	-2.388	Highly Destabilizing	0.949	D	0.815	deleterious	D	0.539326623	None	None	N
V/H	0.9944	likely_pathogenic	0.9927	pathogenic	-2.338	Highly Destabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
V/I	0.0915	likely_benign	0.0925	benign	-0.075	Destabilizing	0.008	N	0.227	neutral	N	0.483601011	None	None	N
V/K	0.9886	likely_pathogenic	0.9849	pathogenic	-1.403	Destabilizing	0.961	D	0.802	deleterious	None	None	None	None	N
V/L	0.3476	ambiguous	0.3421	ambiguous	-0.075	Destabilizing	0.003	N	0.289	neutral	N	0.492254993	None	None	N
V/M	0.4968	ambiguous	0.4885	ambiguous	-0.335	Destabilizing	0.923	D	0.667	neutral	None	None	None	None	N
V/N	0.9837	likely_pathogenic	0.9777	pathogenic	-1.912	Destabilizing	0.987	D	0.833	deleterious	None	None	None	None	N
V/P	0.992	likely_pathogenic	0.9903	pathogenic	-0.621	Destabilizing	0.987	D	0.789	deleterious	None	None	None	None	N
V/Q	0.9804	likely_pathogenic	0.9733	pathogenic	-1.583	Destabilizing	0.987	D	0.809	deleterious	None	None	None	None	N
V/R	0.9843	likely_pathogenic	0.978	pathogenic	-1.605	Destabilizing	0.961	D	0.824	deleterious	None	None	None	None	N
V/S	0.9569	likely_pathogenic	0.9429	pathogenic	-2.56	Highly Destabilizing	0.961	D	0.785	deleterious	None	None	None	None	N
V/T	0.8776	likely_pathogenic	0.8426	pathogenic	-2.087	Highly Destabilizing	0.775	D	0.686	prob.neutral	None	None	None	None	N
V/W	0.9964	likely_pathogenic	0.9956	pathogenic	-1.572	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	N
V/Y	0.9853	likely_pathogenic	0.9818	pathogenic	-1.147	Destabilizing	0.961	D	0.759	deleterious	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.