TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22543	67852;67853;67854	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
N2AB	20902	62929;62930;62931	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
N2A	19975	60148;60149;60150	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
N2B	13478	40657;40658;40659	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
Novex-1	13603	41032;41033;41034	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
Novex-2	13670	41233;41234;41235	chr2:178579570;178579569;178579568	chr2:179444297;179444296;179444295
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: Fn3-51
• Domain position: 93
• Structural Position: 132
• Q(SASA): 0.9604
• 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/N	rs1283302985	0.333	1.0	N	0.808	0.397	0.39843156188	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs1283302985	0.333	1.0	N	0.808	0.397	0.39843156188	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	2.41324E-05	0	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
D/A	0.6141	likely_pathogenic	0.6254	pathogenic	-0.182	Destabilizing	1.0	D	0.769	deleterious	N	0.481805216	None	None	N
D/C	0.931	likely_pathogenic	0.9423	pathogenic	0.092	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/E	0.3623	ambiguous	0.3441	ambiguous	-0.286	Destabilizing	0.999	D	0.517	neutral	N	0.481433071	None	None	N
D/F	0.9597	likely_pathogenic	0.9638	pathogenic	-0.246	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/G	0.5001	ambiguous	0.5207	ambiguous	-0.354	Destabilizing	1.0	D	0.811	deleterious	N	0.504682411	None	None	N
D/H	0.7983	likely_pathogenic	0.825	pathogenic	-0.066	Destabilizing	1.0	D	0.884	deleterious	N	0.505949859	None	None	N
D/I	0.895	likely_pathogenic	0.9001	pathogenic	0.213	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
D/K	0.8547	likely_pathogenic	0.858	pathogenic	0.341	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
D/L	0.8669	likely_pathogenic	0.8718	pathogenic	0.213	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
D/M	0.942	likely_pathogenic	0.9432	pathogenic	0.316	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
D/N	0.2593	likely_benign	0.2589	benign	0.144	Stabilizing	1.0	D	0.808	deleterious	N	0.491805168	None	None	N
D/P	0.9269	likely_pathogenic	0.9408	pathogenic	0.103	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
D/Q	0.815	likely_pathogenic	0.8185	pathogenic	0.156	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
D/R	0.8941	likely_pathogenic	0.9002	pathogenic	0.469	Stabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
D/S	0.4509	ambiguous	0.4586	ambiguous	0.033	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
D/T	0.7283	likely_pathogenic	0.7269	pathogenic	0.161	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/V	0.7483	likely_pathogenic	0.7559	pathogenic	0.103	Stabilizing	1.0	D	0.805	deleterious	N	0.505949859	None	None	N
D/W	0.9853	likely_pathogenic	0.988	pathogenic	-0.169	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
D/Y	0.736	likely_pathogenic	0.7558	pathogenic	-0.023	Destabilizing	1.0	D	0.841	deleterious	N	0.506203348	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.