TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26267	79024;79025;79026	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
N2AB	24626	74101;74102;74103	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
N2A	23699	71320;71321;71322	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
N2B	17202	51829;51830;51831	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
Novex-1	17327	52204;52205;52206	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
Novex-2	17394	52405;52406;52407	chr2:178567333;178567332;178567331	chr2:179432060;179432059;179432058
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-137
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.5045
• 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/K	None	None	0.048	N	0.291	0.134	0.194818534648	gnomAD-4.0.0	1.37705E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80407E-06	0	0
R/S	rs1373203200	None	0.104	N	0.393	0.385	0.280987212366	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/S	rs1373203200	None	0.104	N	0.393	0.385	0.280987212366	gnomAD-4.0.0	6.57454E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47102E-05	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	0.3718	ambiguous	0.3046	benign	-1.25	Destabilizing	0.063	N	0.331	neutral	None	None	None	None	N
R/C	0.1262	likely_benign	0.1135	benign	-1.287	Destabilizing	0.942	D	0.557	neutral	None	None	None	None	N
R/D	0.7377	likely_pathogenic	0.6647	pathogenic	-0.252	Destabilizing	0.134	N	0.457	neutral	None	None	None	None	N
R/E	0.2932	likely_benign	0.2472	benign	-0.17	Destabilizing	0.001	N	0.182	neutral	None	None	None	None	N
R/F	0.4776	ambiguous	0.4096	ambiguous	-1.399	Destabilizing	0.842	D	0.607	neutral	None	None	None	None	N
R/G	0.3676	ambiguous	0.3094	benign	-1.485	Destabilizing	0.189	N	0.459	neutral	N	0.490354046	None	None	N
R/H	0.0763	likely_benign	0.0709	benign	-1.6	Destabilizing	0.002	N	0.239	neutral	None	None	None	None	N
R/I	0.1611	likely_benign	0.141	benign	-0.628	Destabilizing	0.104	N	0.458	neutral	N	0.450750379	None	None	N
R/K	0.0655	likely_benign	0.0634	benign	-1.164	Destabilizing	0.048	N	0.291	neutral	N	0.409439687	None	None	N
R/L	0.1631	likely_benign	0.1399	benign	-0.628	Destabilizing	0.063	N	0.423	neutral	None	None	None	None	N
R/M	0.1812	likely_benign	0.1576	benign	-0.731	Destabilizing	0.842	D	0.541	neutral	None	None	None	None	N
R/N	0.4742	ambiguous	0.4043	ambiguous	-0.529	Destabilizing	0.236	N	0.397	neutral	None	None	None	None	N
R/P	0.9634	likely_pathogenic	0.9527	pathogenic	-0.818	Destabilizing	0.603	D	0.557	neutral	None	None	None	None	N
R/Q	0.0855	likely_benign	0.08	benign	-0.882	Destabilizing	0.004	N	0.205	neutral	None	None	None	None	N
R/S	0.3961	ambiguous	0.326	benign	-1.452	Destabilizing	0.104	N	0.393	neutral	N	0.468085346	None	None	N
R/T	0.1248	likely_benign	0.1025	benign	-1.215	Destabilizing	0.001	N	0.27	neutral	N	0.408959684	None	None	N
R/V	0.2059	likely_benign	0.172	benign	-0.818	Destabilizing	0.001	N	0.42	neutral	None	None	None	None	N
R/W	0.1962	likely_benign	0.1671	benign	-1.013	Destabilizing	0.984	D	0.567	neutral	None	None	None	None	N
R/Y	0.3452	ambiguous	0.2951	benign	-0.714	Destabilizing	0.428	N	0.61	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.