TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8513	25762;25763;25764	chr2:178717197;178717196;178717195	chr2:179581924;179581923;179581922
N2AB	8196	24811;24812;24813	chr2:178717197;178717196;178717195	chr2:179581924;179581923;179581922
N2A	7269	22030;22031;22032	chr2:178717197;178717196;178717195	chr2:179581924;179581923;179581922
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-70
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.058
• 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
L/P	None	None	1.0	D	0.909	0.862	0.922627982565	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-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	0.9271	likely_pathogenic	0.9432	pathogenic	-2.106	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
L/C	0.9259	likely_pathogenic	0.9442	pathogenic	-1.597	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-2.906	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/E	0.9978	likely_pathogenic	0.9983	pathogenic	-2.583	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/F	0.6106	likely_pathogenic	0.7058	pathogenic	-1.314	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/G	0.9902	likely_pathogenic	0.9929	pathogenic	-2.709	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/H	0.9941	likely_pathogenic	0.9955	pathogenic	-2.717	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/I	0.2227	likely_benign	0.2838	benign	-0.3	Destabilizing	0.994	D	0.651	neutral	None	None	None	None	N
L/K	0.9975	likely_pathogenic	0.998	pathogenic	-1.541	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/M	0.329	likely_benign	0.3832	ambiguous	-0.627	Destabilizing	0.988	D	0.589	neutral	D	0.526978446	None	None	N
L/N	0.9978	likely_pathogenic	0.9983	pathogenic	-2.25	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/P	0.9987	likely_pathogenic	0.999	pathogenic	-0.892	Destabilizing	1.0	D	0.909	deleterious	D	0.5833059	None	None	N
L/Q	0.9891	likely_pathogenic	0.9916	pathogenic	-1.846	Destabilizing	1.0	D	0.909	deleterious	D	0.5833059	None	None	N
L/R	0.9922	likely_pathogenic	0.9936	pathogenic	-1.856	Destabilizing	1.0	D	0.892	deleterious	D	0.5833059	None	None	N
L/S	0.9939	likely_pathogenic	0.9955	pathogenic	-2.777	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
L/T	0.9769	likely_pathogenic	0.9833	pathogenic	-2.276	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
L/V	0.2143	likely_benign	0.2612	benign	-0.892	Destabilizing	0.994	D	0.679	prob.neutral	D	0.536929173	None	None	N
L/W	0.9797	likely_pathogenic	0.9873	pathogenic	-1.745	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
L/Y	0.9769	likely_pathogenic	0.9852	pathogenic	-1.447	Destabilizing	1.0	D	0.839	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.