TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7573	22942;22943;22944	chr2:178721946;178721945;178721944	chr2:179586673;179586672;179586671
N2AB	7256	21991;21992;21993	chr2:178721946;178721945;178721944	chr2:179586673;179586672;179586671
N2A	6329	19210;19211;19212	chr2:178721946;178721945;178721944	chr2:179586673;179586672;179586671
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: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-60
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3949
• 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
R/S	None	None	0.514	N	0.496	0.367	0.319114376414	gnomAD-4.0.0	6.84324E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87266E-05	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	0.4651	ambiguous	0.5282	ambiguous	-1.068	Destabilizing	0.737	D	0.455	neutral	None	None	None	None	N
R/C	0.2159	likely_benign	0.2126	benign	-1.022	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	N
R/D	0.7762	likely_pathogenic	0.831	pathogenic	-0.221	Destabilizing	0.773	D	0.558	neutral	None	None	None	None	N
R/E	0.4023	ambiguous	0.4406	ambiguous	-0.092	Destabilizing	0.083	N	0.315	neutral	None	None	None	None	N
R/F	0.6292	likely_pathogenic	0.6846	pathogenic	-0.895	Destabilizing	0.98	D	0.542	neutral	None	None	None	None	N
R/G	0.3976	ambiguous	0.4627	ambiguous	-1.386	Destabilizing	0.912	D	0.561	neutral	N	0.498218085	None	None	N
R/H	0.0843	likely_benign	0.0923	benign	-1.556	Destabilizing	0.993	D	0.485	neutral	None	None	None	None	N
R/I	0.3034	likely_benign	0.3297	benign	-0.206	Destabilizing	0.064	N	0.519	neutral	N	0.447422072	None	None	N
R/K	0.0941	likely_benign	0.0918	benign	-1.073	Destabilizing	0.028	N	0.301	neutral	N	0.477302262	None	None	N
R/L	0.2725	likely_benign	0.3241	benign	-0.206	Destabilizing	0.584	D	0.493	neutral	None	None	None	None	N
R/M	0.265	likely_benign	0.2923	benign	-0.454	Destabilizing	0.98	D	0.527	neutral	None	None	None	None	N
R/N	0.5617	ambiguous	0.6078	pathogenic	-0.503	Destabilizing	0.932	D	0.455	neutral	None	None	None	None	N
R/P	0.9695	likely_pathogenic	0.9814	pathogenic	-0.474	Destabilizing	0.977	D	0.579	neutral	None	None	None	None	N
R/Q	0.0904	likely_benign	0.097	benign	-0.701	Destabilizing	0.872	D	0.459	neutral	None	None	None	None	N
R/S	0.4496	ambiguous	0.518	ambiguous	-1.359	Destabilizing	0.514	D	0.496	neutral	N	0.487172539	None	None	N
R/T	0.1691	likely_benign	0.1924	benign	-1.043	Destabilizing	0.028	N	0.382	neutral	N	0.432873907	None	None	N
R/V	0.3643	ambiguous	0.3983	ambiguous	-0.474	Destabilizing	0.584	D	0.503	neutral	None	None	None	None	N
R/W	0.248	likely_benign	0.2986	benign	-0.478	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
R/Y	0.4594	ambiguous	0.5166	ambiguous	-0.199	Destabilizing	0.993	D	0.553	neutral	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.