TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16605	50038;50039;50040	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
N2AB	14964	45115;45116;45117	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
N2A	14037	42334;42335;42336	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
N2B	7540	22843;22844;22845	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
Novex-1	7665	23218;23219;23220	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
Novex-2	7732	23419;23420;23421	chr2:178612908;178612907;178612906	chr2:179477635;179477634;179477633
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: Fn3-8
• Domain position: 55
• Structural Position: 77
• Q(SASA): 0.0969
• 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/I	None	None	0.02	N	0.22	0.132	0.497152477365	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.5847	likely_pathogenic	0.6322	pathogenic	-1.761	Destabilizing	0.939	D	0.519	neutral	N	0.463384175	None	None	N
V/C	0.8715	likely_pathogenic	0.8558	pathogenic	-1.224	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
V/D	0.9098	likely_pathogenic	0.9559	pathogenic	-1.829	Destabilizing	0.997	D	0.753	deleterious	N	0.496625629	None	None	N
V/E	0.8286	likely_pathogenic	0.8974	pathogenic	-1.673	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
V/F	0.4177	ambiguous	0.485	ambiguous	-1.092	Destabilizing	0.982	D	0.687	prob.neutral	D	0.525288029	None	None	N
V/G	0.7198	likely_pathogenic	0.8215	pathogenic	-2.254	Highly Destabilizing	0.997	D	0.755	deleterious	N	0.464430381	None	None	N
V/H	0.9323	likely_pathogenic	0.9559	pathogenic	-1.978	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
V/I	0.0767	likely_benign	0.0719	benign	-0.428	Destabilizing	0.02	N	0.22	neutral	N	0.448122508	None	None	N
V/K	0.8681	likely_pathogenic	0.9276	pathogenic	-1.355	Destabilizing	0.993	D	0.679	prob.neutral	None	None	None	None	N
V/L	0.3855	ambiguous	0.3883	ambiguous	-0.428	Destabilizing	0.76	D	0.453	neutral	N	0.47742725	None	None	N
V/M	0.3165	likely_benign	0.3377	benign	-0.382	Destabilizing	0.986	D	0.669	neutral	None	None	None	None	N
V/N	0.7963	likely_pathogenic	0.858	pathogenic	-1.45	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
V/P	0.9412	likely_pathogenic	0.9581	pathogenic	-0.841	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
V/Q	0.8353	likely_pathogenic	0.8933	pathogenic	-1.376	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
V/R	0.8566	likely_pathogenic	0.9227	pathogenic	-1.161	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
V/S	0.6955	likely_pathogenic	0.772	pathogenic	-2.106	Highly Destabilizing	0.993	D	0.687	prob.neutral	None	None	None	None	N
V/T	0.574	likely_pathogenic	0.6324	pathogenic	-1.807	Destabilizing	0.953	D	0.629	neutral	None	None	None	None	N
V/W	0.9717	likely_pathogenic	0.9806	pathogenic	-1.519	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
V/Y	0.8755	likely_pathogenic	0.9106	pathogenic	-1.126	Destabilizing	0.998	D	0.679	prob.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.