TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9656	29191;29192;29193	chr2:178707601;178707600;178707599	chr2:179572328;179572327;179572326
N2AB	9339	28240;28241;28242	chr2:178707601;178707600;178707599	chr2:179572328;179572327;179572326
N2A	8412	25459;25460;25461	chr2:178707601;178707600;178707599	chr2:179572328;179572327;179572326
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-82
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1816
• 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	rs1064797277	None	0.946	None	0.804	0.589	0.606648057779	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	2.98704E-05	0	None	0	0	None	0	0	0	0	1.65662E-05

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	0.6984	likely_pathogenic	0.5868	pathogenic	0.016	Stabilizing	0.898	D	0.859	deleterious	None	None	None	None	N
D/C	0.9583	likely_pathogenic	0.9356	pathogenic	0.039	Stabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
D/E	0.4827	ambiguous	0.5451	ambiguous	-0.541	Destabilizing	0.016	N	0.351	neutral	None	None	None	None	N
D/F	0.9333	likely_pathogenic	0.9035	pathogenic	0.745	Stabilizing	0.998	D	0.915	deleterious	None	None	None	None	N
D/G	0.7927	likely_pathogenic	0.7167	pathogenic	-0.377	Destabilizing	0.834	D	0.807	deleterious	None	None	None	None	N
D/H	0.7937	likely_pathogenic	0.7494	pathogenic	0.605	Stabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
D/I	0.8973	likely_pathogenic	0.8507	pathogenic	1.058	Stabilizing	0.979	D	0.906	deleterious	None	None	None	None	N
D/K	0.9363	likely_pathogenic	0.9299	pathogenic	0.289	Stabilizing	0.921	D	0.829	deleterious	None	None	None	None	N
D/L	0.9096	likely_pathogenic	0.8666	pathogenic	1.058	Stabilizing	0.959	D	0.903	deleterious	None	None	None	None	N
D/M	0.9571	likely_pathogenic	0.9395	pathogenic	1.265	Stabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
D/N	0.4743	ambiguous	0.3832	ambiguous	-0.541	Destabilizing	0.946	D	0.804	deleterious	None	None	None	None	N
D/P	0.9893	likely_pathogenic	0.9829	pathogenic	0.738	Stabilizing	0.979	D	0.855	deleterious	None	None	None	None	N
D/Q	0.8408	likely_pathogenic	0.8325	pathogenic	-0.301	Destabilizing	0.921	D	0.809	deleterious	None	None	None	None	N
D/R	0.9489	likely_pathogenic	0.9368	pathogenic	0.474	Stabilizing	0.959	D	0.897	deleterious	None	None	None	None	N
D/S	0.562	ambiguous	0.4552	ambiguous	-0.71	Destabilizing	0.769	D	0.732	prob.delet.	None	None	None	None	N
D/T	0.841	likely_pathogenic	0.7784	pathogenic	-0.349	Destabilizing	0.959	D	0.837	deleterious	None	None	None	None	N
D/V	0.7665	likely_pathogenic	0.6942	pathogenic	0.738	Stabilizing	0.946	D	0.907	deleterious	None	None	None	None	N
D/W	0.9913	likely_pathogenic	0.9871	pathogenic	0.966	Stabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
D/Y	0.7325	likely_pathogenic	0.6556	pathogenic	1.049	Stabilizing	0.998	D	0.916	deleterious	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.