TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25358	76297;76298;76299	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
N2AB	23717	71374;71375;71376	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
N2A	22790	68593;68594;68595	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
N2B	16293	49102;49103;49104	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
Novex-1	16418	49477;49478;49479	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
Novex-2	16485	49678;49679;49680	chr2:178570060;178570059;178570058	chr2:179434787;179434786;179434785
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: Fn3-72
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3079
• 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/V	None	None	0.013	N	0.135	0.048	0.141422826196	gnomAD-4.0.0	1.59212E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	0	None	0	0	0	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	0.1838	likely_benign	0.1966	benign	-1.269	Destabilizing	0.345	N	0.379	neutral	None	None	None	None	N
L/C	0.4856	ambiguous	0.5014	ambiguous	-0.874	Destabilizing	0.991	D	0.393	neutral	None	None	None	None	N
L/D	0.7242	likely_pathogenic	0.7185	pathogenic	-0.393	Destabilizing	0.39	N	0.485	neutral	None	None	None	None	N
L/E	0.445	ambiguous	0.4341	ambiguous	-0.388	Destabilizing	0.561	D	0.503	neutral	None	None	None	None	N
L/F	0.2049	likely_benign	0.209	benign	-0.721	Destabilizing	0.818	D	0.43	neutral	None	None	None	None	N
L/G	0.4225	ambiguous	0.4331	ambiguous	-1.57	Destabilizing	0.561	D	0.476	neutral	None	None	None	None	N
L/H	0.2734	likely_benign	0.2565	benign	-0.658	Destabilizing	0.972	D	0.511	neutral	None	None	None	None	N
L/I	0.1028	likely_benign	0.1112	benign	-0.533	Destabilizing	0.004	N	0.24	neutral	None	None	None	None	N
L/K	0.2678	likely_benign	0.2474	benign	-0.842	Destabilizing	0.561	D	0.467	neutral	None	None	None	None	N
L/M	0.1107	likely_benign	0.1249	benign	-0.551	Destabilizing	0.772	D	0.457	neutral	N	0.473116758	None	None	N
L/N	0.3109	likely_benign	0.3342	benign	-0.721	Destabilizing	0.017	N	0.412	neutral	None	None	None	None	N
L/P	0.1001	likely_benign	0.1	benign	-0.746	Destabilizing	0.001	N	0.376	neutral	N	0.400942342	None	None	N
L/Q	0.1606	likely_benign	0.1481	benign	-0.848	Destabilizing	0.873	D	0.469	neutral	N	0.494007219	None	None	N
L/R	0.2307	likely_benign	0.1956	benign	-0.306	Destabilizing	0.873	D	0.459	neutral	N	0.445981198	None	None	N
L/S	0.2624	likely_benign	0.259	benign	-1.355	Destabilizing	0.39	N	0.428	neutral	None	None	None	None	N
L/T	0.1641	likely_benign	0.1769	benign	-1.232	Destabilizing	0.007	N	0.178	neutral	None	None	None	None	N
L/V	0.0925	likely_benign	0.0964	benign	-0.746	Destabilizing	0.013	N	0.135	neutral	N	0.440116806	None	None	N
L/W	0.4134	ambiguous	0.3755	ambiguous	-0.765	Destabilizing	0.991	D	0.521	neutral	None	None	None	None	N
L/Y	0.4194	ambiguous	0.4233	ambiguous	-0.546	Destabilizing	0.965	D	0.41	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.