TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32923	98992;98993;98994	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
N2AB	31282	94069;94070;94071	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
N2A	30355	91288;91289;91290	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
N2B	23858	71797;71798;71799	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
Novex-1	23983	72172;72173;72174	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
Novex-2	24050	72373;72374;72375	chr2:178539168;178539167;178539166	chr2:179403895;179403894;179403893
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-128
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.6668
• 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
D/G	None	None	1.0	N	0.616	0.433	0.36355261348	gnomAD-4.0.0	6.84209E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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
D/A	0.5127	ambiguous	0.4782	ambiguous	-0.303	Destabilizing	1.0	D	0.657	neutral	N	0.509571317	None	None	N
D/C	0.8542	likely_pathogenic	0.8721	pathogenic	0.105	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
D/E	0.3202	likely_benign	0.3312	benign	-0.451	Destabilizing	1.0	D	0.383	neutral	N	0.508416524	None	None	N
D/F	0.7926	likely_pathogenic	0.7538	pathogenic	-0.36	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
D/G	0.4539	ambiguous	0.4451	ambiguous	-0.523	Destabilizing	1.0	D	0.616	neutral	N	0.47726736	None	None	N
D/H	0.6307	likely_pathogenic	0.569	pathogenic	-0.458	Destabilizing	1.0	D	0.569	neutral	N	0.471669077	None	None	N
D/I	0.7767	likely_pathogenic	0.753	pathogenic	0.234	Stabilizing	1.0	D	0.658	neutral	None	None	None	None	N
D/K	0.8151	likely_pathogenic	0.8044	pathogenic	0.12	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
D/L	0.7715	likely_pathogenic	0.7241	pathogenic	0.234	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
D/M	0.8899	likely_pathogenic	0.8559	pathogenic	0.527	Stabilizing	1.0	D	0.656	neutral	None	None	None	None	N
D/N	0.2171	likely_benign	0.1864	benign	-0.097	Destabilizing	1.0	D	0.606	neutral	N	0.494332506	None	None	N
D/P	0.9893	likely_pathogenic	0.9868	pathogenic	0.078	Stabilizing	1.0	D	0.65	neutral	None	None	None	None	N
D/Q	0.7272	likely_pathogenic	0.6962	pathogenic	-0.059	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
D/R	0.8161	likely_pathogenic	0.7887	pathogenic	0.197	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/S	0.3274	likely_benign	0.295	benign	-0.223	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
D/T	0.5899	likely_pathogenic	0.5608	ambiguous	-0.057	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
D/V	0.5681	likely_pathogenic	0.5399	ambiguous	0.078	Stabilizing	1.0	D	0.691	prob.neutral	N	0.470177016	None	None	N
D/W	0.9544	likely_pathogenic	0.9341	pathogenic	-0.282	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
D/Y	0.388	ambiguous	0.3541	ambiguous	-0.146	Destabilizing	1.0	D	0.614	neutral	N	0.472477153	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.