TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6050	18373;18374;18375	chr2:178730252;178730251;178730250	chr2:179594979;179594978;179594977
N2AB	5733	17422;17423;17424	chr2:178730252;178730251;178730250	chr2:179594979;179594978;179594977
N2A	4806	14641;14642;14643	chr2:178730252;178730251;178730250	chr2:179594979;179594978;179594977
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-44
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.548
• 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
K/E	None	None	0.811	N	0.483	0.23	0.416454006429	gnomAD-4.0.0	6.8442E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99594E-07	0	0
K/Q	rs2080195973	None	0.211	N	0.248	0.128	0.340273420219	gnomAD-4.0.0	6.8442E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99594E-07	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
K/A	0.3282	likely_benign	0.2784	benign	-0.138	Destabilizing	0.919	D	0.471	neutral	None	None	None	None	N
K/C	0.7571	likely_pathogenic	0.7046	pathogenic	-0.389	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
K/D	0.5467	ambiguous	0.464	ambiguous	-0.062	Destabilizing	0.976	D	0.395	neutral	None	None	None	None	N
K/E	0.1209	likely_benign	0.1101	benign	-0.007	Destabilizing	0.811	D	0.483	neutral	N	0.486516391	None	None	N
K/F	0.7537	likely_pathogenic	0.6955	pathogenic	-0.082	Destabilizing	0.988	D	0.591	neutral	None	None	None	None	N
K/G	0.4993	ambiguous	0.4497	ambiguous	-0.408	Destabilizing	0.919	D	0.413	neutral	None	None	None	None	N
K/H	0.3202	likely_benign	0.2939	benign	-0.627	Destabilizing	0.997	D	0.474	neutral	None	None	None	None	N
K/I	0.2854	likely_benign	0.2306	benign	0.516	Stabilizing	0.938	D	0.504	neutral	D	0.527192364	None	None	N
K/L	0.3477	ambiguous	0.3009	benign	0.516	Stabilizing	0.851	D	0.438	neutral	None	None	None	None	N
K/M	0.2089	likely_benign	0.1831	benign	0.133	Stabilizing	0.988	D	0.475	neutral	None	None	None	None	N
K/N	0.3899	ambiguous	0.3144	benign	-0.164	Destabilizing	0.968	D	0.409	neutral	D	0.528288443	None	None	N
K/P	0.939	likely_pathogenic	0.9291	pathogenic	0.328	Stabilizing	0.988	D	0.463	neutral	None	None	None	None	N
K/Q	0.1038	likely_benign	0.1016	benign	-0.241	Destabilizing	0.211	N	0.248	neutral	N	0.482841368	None	None	N
K/R	0.0834	likely_benign	0.0831	benign	-0.319	Destabilizing	0.811	D	0.432	neutral	N	0.499928405	None	None	N
K/S	0.4113	ambiguous	0.3418	ambiguous	-0.636	Destabilizing	0.919	D	0.439	neutral	None	None	None	None	N
K/T	0.1532	likely_benign	0.1273	benign	-0.412	Destabilizing	0.896	D	0.422	neutral	N	0.48690318	None	None	N
K/V	0.2526	likely_benign	0.2092	benign	0.328	Stabilizing	0.261	N	0.298	neutral	None	None	None	None	N
K/W	0.7493	likely_pathogenic	0.7349	pathogenic	-0.085	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
K/Y	0.6279	likely_pathogenic	0.5841	pathogenic	0.225	Stabilizing	0.996	D	0.537	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.