TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31771	95536;95537;95538	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
N2AB	30130	90613;90614;90615	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
N2A	29203	87832;87833;87834	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
N2B	22706	68341;68342;68343	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
Novex-1	22831	68716;68717;68718	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
Novex-2	22898	68917;68918;68919	chr2:178545925;178545924;178545923	chr2:179410652;179410651;179410650
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-119
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.807
• 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/K	rs397517760	0.052	0.001	N	0.212	0.084	0.124217242631	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	1.29132E-04	0	None	0	0	None	0	None	0	0	0
R/K	rs397517760	0.052	0.001	N	0.212	0.084	0.124217242631	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs397517760	0.052	0.001	N	0.212	0.084	0.124217242631	gnomAD-4.0.0	1.9714E-05	None	None	None	None	I	None	7.23729E-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
R/A	0.5718	likely_pathogenic	0.7134	pathogenic	-0.03	Destabilizing	0.404	N	0.461	neutral	None	None	None	None	I
R/C	0.3287	likely_benign	0.3948	ambiguous	-0.309	Destabilizing	0.991	D	0.637	neutral	None	None	None	None	I
R/D	0.7497	likely_pathogenic	0.8563	pathogenic	-0.312	Destabilizing	0.826	D	0.485	neutral	None	None	None	None	I
R/E	0.5845	likely_pathogenic	0.7252	pathogenic	-0.277	Destabilizing	0.404	N	0.482	neutral	None	None	None	None	I
R/F	0.8391	likely_pathogenic	0.8832	pathogenic	-0.353	Destabilizing	0.967	D	0.596	neutral	None	None	None	None	I
R/G	0.2467	likely_benign	0.3827	ambiguous	-0.161	Destabilizing	0.505	D	0.467	neutral	N	0.406361231	None	None	I
R/H	0.138	likely_benign	0.1662	benign	-0.586	Destabilizing	0.906	D	0.517	neutral	None	None	None	None	I
R/I	0.7345	likely_pathogenic	0.8067	pathogenic	0.267	Stabilizing	0.906	D	0.596	neutral	None	None	None	None	I
R/K	0.1118	likely_benign	0.1278	benign	-0.228	Destabilizing	0.001	N	0.212	neutral	N	0.391533425	None	None	I
R/L	0.5204	ambiguous	0.62	pathogenic	0.267	Stabilizing	0.575	D	0.467	neutral	None	None	None	None	I
R/M	0.5749	likely_pathogenic	0.6824	pathogenic	-0.12	Destabilizing	0.988	D	0.509	neutral	N	0.486586204	None	None	I
R/N	0.591	likely_pathogenic	0.7065	pathogenic	-0.128	Destabilizing	0.826	D	0.484	neutral	None	None	None	None	I
R/P	0.8076	likely_pathogenic	0.8968	pathogenic	0.185	Stabilizing	0.906	D	0.553	neutral	None	None	None	None	I
R/Q	0.1558	likely_benign	0.2012	benign	-0.182	Destabilizing	0.704	D	0.517	neutral	None	None	None	None	I
R/S	0.5984	likely_pathogenic	0.7175	pathogenic	-0.331	Destabilizing	0.338	N	0.477	neutral	N	0.481403281	None	None	I
R/T	0.484	ambiguous	0.6323	pathogenic	-0.195	Destabilizing	0.505	D	0.464	neutral	N	0.46797497	None	None	I
R/V	0.7381	likely_pathogenic	0.8082	pathogenic	0.185	Stabilizing	0.826	D	0.57	neutral	None	None	None	None	I
R/W	0.3817	ambiguous	0.4758	ambiguous	-0.521	Destabilizing	0.988	D	0.663	neutral	N	0.498360583	None	None	I
R/Y	0.6002	likely_pathogenic	0.6758	pathogenic	-0.125	Destabilizing	0.967	D	0.555	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.