TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30366	91321;91322;91323	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
N2AB	28725	86398;86399;86400	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
N2A	27798	83617;83618;83619	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
N2B	21301	64126;64127;64128	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
Novex-1	21426	64501;64502;64503	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
Novex-2	21493	64702;64703;64704	chr2:178551804;178551803;178551802	chr2:179416531;179416530;179416529
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-109
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.6159
• Predicted PPI site: I

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
R/G	None	None	1.0	N	0.625	0.332	0.508755544265	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85796E-06	0	0
R/I	None	None	1.0	N	0.694	0.436	0.586756053714	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	2.773E-05	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
R/A	0.8513	likely_pathogenic	0.8236	pathogenic	-0.636	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	I
R/C	0.5262	ambiguous	0.5023	ambiguous	-0.629	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
R/D	0.9723	likely_pathogenic	0.9668	pathogenic	0.01	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
R/E	0.8255	likely_pathogenic	0.806	pathogenic	0.107	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
R/F	0.9391	likely_pathogenic	0.9298	pathogenic	-0.701	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
R/G	0.7379	likely_pathogenic	0.6991	pathogenic	-0.889	Destabilizing	1.0	D	0.625	neutral	N	0.479653842	None	None	I
R/H	0.3397	likely_benign	0.3124	benign	-1.318	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
R/I	0.7369	likely_pathogenic	0.7184	pathogenic	0.02	Stabilizing	1.0	D	0.694	prob.neutral	N	0.496007374	None	None	I
R/K	0.159	likely_benign	0.1475	benign	-0.566	Destabilizing	0.997	D	0.527	neutral	N	0.419122671	None	None	I
R/L	0.7085	likely_pathogenic	0.6703	pathogenic	0.02	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	I
R/M	0.7325	likely_pathogenic	0.6985	pathogenic	-0.304	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	I
R/N	0.9345	likely_pathogenic	0.9215	pathogenic	-0.145	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
R/P	0.9473	likely_pathogenic	0.9459	pathogenic	-0.178	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
R/Q	0.2374	likely_benign	0.2169	benign	-0.316	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
R/S	0.9239	likely_pathogenic	0.9097	pathogenic	-0.824	Destabilizing	1.0	D	0.649	neutral	N	0.477093539	None	None	I
R/T	0.815	likely_pathogenic	0.796	pathogenic	-0.56	Destabilizing	1.0	D	0.647	neutral	N	0.476208105	None	None	I
R/V	0.814	likely_pathogenic	0.7994	pathogenic	-0.178	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
R/W	0.5809	likely_pathogenic	0.5565	ambiguous	-0.504	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
R/Y	0.8341	likely_pathogenic	0.8129	pathogenic	-0.166	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I

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.