TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28876	86851;86852;86853	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
N2AB	27235	81928;81929;81930	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
N2A	26308	79147;79148;79149	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
N2B	19811	59656;59657;59658	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
Novex-1	19936	60031;60032;60033	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
Novex-2	20003	60232;60233;60234	chr2:178559506;178559505;178559504	chr2:179424233;179424232;179424231
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-98
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7146
• 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
P/L	rs987601709	None	None	N	0.365	0.227	0.415947407303	gnomAD-4.0.0	6.8424E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99509E-07	0	0
P/S	rs1322696753	-0.201	0.062	N	0.412	0.205	0.18274738541	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	3.27E-05	None	0	0	0
P/S	rs1322696753	-0.201	0.062	N	0.412	0.205	0.18274738541	gnomAD-4.0.0	6.36568E-06	None	None	None	None	I	None	0	2.28624E-05	None	0	0	None	0	0	0	4.29873E-05	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
P/A	0.0749	likely_benign	0.0556	benign	-0.761	Destabilizing	None	N	0.14	neutral	D	0.525447633	None	None	I
P/C	0.5737	likely_pathogenic	0.4829	ambiguous	-0.551	Destabilizing	0.824	D	0.494	neutral	None	None	None	None	I
P/D	0.6734	likely_pathogenic	0.5466	ambiguous	-0.658	Destabilizing	0.38	N	0.427	neutral	None	None	None	None	I
P/E	0.4485	ambiguous	0.3361	benign	-0.778	Destabilizing	0.081	N	0.393	neutral	None	None	None	None	I
P/F	0.5606	ambiguous	0.4482	ambiguous	-0.993	Destabilizing	0.235	N	0.505	neutral	None	None	None	None	I
P/G	0.4143	ambiguous	0.3216	benign	-0.916	Destabilizing	0.081	N	0.45	neutral	None	None	None	None	I
P/H	0.2792	likely_benign	0.2278	benign	-0.498	Destabilizing	0.698	D	0.479	neutral	None	None	None	None	I
P/I	0.2794	likely_benign	0.1957	benign	-0.497	Destabilizing	0.235	N	0.485	neutral	None	None	None	None	I
P/K	0.433	ambiguous	0.3236	benign	-0.607	Destabilizing	0.081	N	0.405	neutral	None	None	None	None	I
P/L	0.1182	likely_benign	0.0933	benign	-0.497	Destabilizing	None	N	0.365	neutral	N	0.493631004	None	None	I
P/M	0.2721	likely_benign	0.2051	benign	-0.305	Destabilizing	0.38	N	0.484	neutral	None	None	None	None	I
P/N	0.4178	ambiguous	0.3198	benign	-0.267	Destabilizing	0.38	N	0.503	neutral	None	None	None	None	I
P/Q	0.1994	likely_benign	0.1512	benign	-0.575	Destabilizing	0.004	N	0.319	neutral	N	0.484703781	None	None	I
P/R	0.2904	likely_benign	0.2211	benign	-0.002	Destabilizing	0.001	N	0.359	neutral	N	0.477399627	None	None	I
P/S	0.1646	likely_benign	0.1211	benign	-0.62	Destabilizing	0.062	N	0.412	neutral	N	0.485842643	None	None	I
P/T	0.1211	likely_benign	0.087	benign	-0.645	Destabilizing	0.062	N	0.451	neutral	N	0.491856577	None	None	I
P/V	0.1696	likely_benign	0.1209	benign	-0.549	Destabilizing	0.081	N	0.447	neutral	None	None	None	None	I
P/W	0.7638	likely_pathogenic	0.6656	pathogenic	-1.058	Destabilizing	0.935	D	0.609	neutral	None	None	None	None	I
P/Y	0.5638	ambiguous	0.4549	ambiguous	-0.768	Destabilizing	0.555	D	0.507	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.