TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23166	69721;69722;69723	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
N2AB	21525	64798;64799;64800	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
N2A	20598	62017;62018;62019	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
N2B	14101	42526;42527;42528	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
Novex-1	14226	42901;42902;42903	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
Novex-2	14293	43102;43103;43104	chr2:178576748;178576747;178576746	chr2:179441475;179441474;179441473
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: Fn3-56
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.1523
• 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/V	None	None	1.0	N	0.699	0.571	0.634044673573	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
D/A	0.8932	likely_pathogenic	0.874	pathogenic	-0.233	Destabilizing	1.0	D	0.711	prob.delet.	N	0.489766209	None	None	N
D/C	0.978	likely_pathogenic	0.9735	pathogenic	0.286	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
D/E	0.8816	likely_pathogenic	0.8759	pathogenic	-0.448	Destabilizing	1.0	D	0.489	neutral	N	0.485954321	None	None	N
D/F	0.9849	likely_pathogenic	0.983	pathogenic	-0.465	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
D/G	0.856	likely_pathogenic	0.8326	pathogenic	-0.448	Destabilizing	1.0	D	0.706	prob.neutral	N	0.519266449	None	None	N
D/H	0.911	likely_pathogenic	0.904	pathogenic	-0.716	Destabilizing	1.0	D	0.665	neutral	N	0.499085053	None	None	N
D/I	0.9645	likely_pathogenic	0.9604	pathogenic	0.285	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	N
D/K	0.9708	likely_pathogenic	0.9672	pathogenic	0.326	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
D/L	0.9634	likely_pathogenic	0.9583	pathogenic	0.285	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
D/M	0.9832	likely_pathogenic	0.9811	pathogenic	0.691	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	N
D/N	0.2494	likely_benign	0.2316	benign	0.084	Stabilizing	1.0	D	0.733	prob.delet.	N	0.51280641	None	None	N
D/P	0.9846	likely_pathogenic	0.982	pathogenic	0.135	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/Q	0.9605	likely_pathogenic	0.9576	pathogenic	0.122	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/R	0.967	likely_pathogenic	0.9634	pathogenic	0.224	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
D/S	0.5898	likely_pathogenic	0.5426	ambiguous	-0.018	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/T	0.7698	likely_pathogenic	0.7112	pathogenic	0.153	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
D/V	0.921	likely_pathogenic	0.9079	pathogenic	0.135	Stabilizing	1.0	D	0.699	prob.neutral	N	0.506642696	None	None	N
D/W	0.9963	likely_pathogenic	0.9962	pathogenic	-0.441	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
D/Y	0.8925	likely_pathogenic	0.8789	pathogenic	-0.25	Destabilizing	1.0	D	0.624	neutral	D	0.542143644	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.