TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30598	92017;92018;92019	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
N2AB	28957	87094;87095;87096	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
N2A	28030	84313;84314;84315	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
N2B	21533	64822;64823;64824	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
Novex-1	21658	65197;65198;65199	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
Novex-2	21725	65398;65399;65400	chr2:178550046;178550045;178550044	chr2:179414773;179414772;179414771
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-149
• Domain position: 67
• Structural Position: 155
• Q(SASA): 0.1324
• 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
T/K	None	None	None	N	0.424	0.205	0.244539031024	gnomAD-4.0.0	6.84254E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15966E-05	0
T/R	rs370342796	None	None	N	0.349	0.092	None	gnomAD-4.0.0	3.42127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49758E-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
T/A	0.0803	likely_benign	0.0779	benign	-1.17	Destabilizing	0.027	N	0.51	neutral	N	0.472674414	None	None	N
T/C	0.2062	likely_benign	0.1953	benign	-0.698	Destabilizing	0.935	D	0.603	neutral	None	None	None	None	N
T/D	0.4935	ambiguous	0.4877	ambiguous	-1.305	Destabilizing	0.149	N	0.575	neutral	None	None	None	None	N
T/E	0.2563	likely_benign	0.2677	benign	-1.065	Destabilizing	0.081	N	0.533	neutral	None	None	None	None	N
T/F	0.1697	likely_benign	0.1617	benign	-0.721	Destabilizing	0.555	D	0.667	neutral	None	None	None	None	N
T/G	0.2102	likely_benign	0.2013	benign	-1.603	Destabilizing	0.081	N	0.583	neutral	None	None	None	None	N
T/H	0.1924	likely_benign	0.1969	benign	-1.534	Destabilizing	0.824	D	0.655	neutral	None	None	None	None	N
T/I	0.1024	likely_benign	0.0911	benign	-0.013	Destabilizing	0.484	N	0.59	neutral	N	0.511584541	None	None	N
T/K	0.169	likely_benign	0.1799	benign	-0.214	Destabilizing	None	N	0.424	neutral	N	0.501714264	None	None	N
T/L	0.083	likely_benign	0.077	benign	-0.013	Destabilizing	0.149	N	0.532	neutral	None	None	None	None	N
T/M	0.073	likely_benign	0.0721	benign	-0.218	Destabilizing	0.935	D	0.607	neutral	None	None	None	None	N
T/N	0.1691	likely_benign	0.1534	benign	-0.97	Destabilizing	0.149	N	0.557	neutral	None	None	None	None	N
T/P	0.8572	likely_pathogenic	0.8473	pathogenic	-0.369	Destabilizing	0.484	N	0.586	neutral	N	0.508175362	None	None	N
T/Q	0.1679	likely_benign	0.1773	benign	-0.676	Destabilizing	0.235	N	0.588	neutral	None	None	None	None	N
T/R	0.1175	likely_benign	0.1213	benign	-0.532	Destabilizing	None	N	0.349	neutral	N	0.501732907	None	None	N
T/S	0.1047	likely_benign	0.0994	benign	-1.238	Destabilizing	0.002	N	0.389	neutral	N	0.464022668	None	None	N
T/V	0.0911	likely_benign	0.0823	benign	-0.369	Destabilizing	0.149	N	0.549	neutral	None	None	None	None	N
T/W	0.4078	ambiguous	0.4222	ambiguous	-0.86	Destabilizing	0.935	D	0.697	prob.neutral	None	None	None	None	N
T/Y	0.2079	likely_benign	0.2009	benign	-0.458	Destabilizing	0.555	D	0.668	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.