TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16511	49756;49757;49758	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
N2AB	14870	44833;44834;44835	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
N2A	13943	42052;42053;42054	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
N2B	7446	22561;22562;22563	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
Novex-1	7571	22936;22937;22938	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
Novex-2	7638	23137;23138;23139	chr2:178613752;178613751;178613276	chr2:179478479;179478478;179478003
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: Fn3-7
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.727
• 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	rs1372771873	0.154	0.003	N	0.288	0.078	0.275215494804	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
R/K	rs1372771873	0.154	0.003	N	0.288	0.078	0.275215494804	gnomAD-4.0.0	1.59581E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43653E-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
R/A	0.9469	likely_pathogenic	0.9086	pathogenic	-0.905	Destabilizing	0.633	D	0.617	neutral	None	None	None	None	N
R/C	0.7213	likely_pathogenic	0.5493	ambiguous	-0.875	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	N
R/D	0.9866	likely_pathogenic	0.9759	pathogenic	-0.053	Destabilizing	0.923	D	0.629	neutral	None	None	None	None	N
R/E	0.9278	likely_pathogenic	0.8803	pathogenic	0.087	Stabilizing	0.633	D	0.602	neutral	None	None	None	None	N
R/F	0.9639	likely_pathogenic	0.9213	pathogenic	-0.72	Destabilizing	0.987	D	0.687	prob.neutral	None	None	None	None	N
R/G	0.9354	likely_pathogenic	0.9023	pathogenic	-1.223	Destabilizing	0.722	D	0.613	neutral	N	0.466423357	None	None	N
R/H	0.4137	ambiguous	0.3119	benign	-1.534	Destabilizing	0.961	D	0.663	neutral	None	None	None	None	N
R/I	0.8236	likely_pathogenic	0.6641	pathogenic	-0.046	Destabilizing	0.949	D	0.687	prob.neutral	N	0.478166988	None	None	N
R/K	0.2759	likely_benign	0.1929	benign	-0.819	Destabilizing	0.003	N	0.288	neutral	N	0.429028767	None	None	N
R/L	0.7798	likely_pathogenic	0.6561	pathogenic	-0.046	Destabilizing	0.775	D	0.613	neutral	None	None	None	None	N
R/M	0.8672	likely_pathogenic	0.7364	pathogenic	-0.412	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	N
R/N	0.9734	likely_pathogenic	0.9522	pathogenic	-0.373	Destabilizing	0.775	D	0.611	neutral	None	None	None	None	N
R/P	0.9663	likely_pathogenic	0.9367	pathogenic	-0.312	Destabilizing	0.961	D	0.695	prob.neutral	None	None	None	None	N
R/Q	0.4309	ambiguous	0.33	benign	-0.5	Destabilizing	0.633	D	0.632	neutral	None	None	None	None	N
R/S	0.9649	likely_pathogenic	0.9418	pathogenic	-1.176	Destabilizing	0.565	D	0.609	neutral	N	0.477276774	None	None	N
R/T	0.8411	likely_pathogenic	0.7277	pathogenic	-0.841	Destabilizing	0.722	D	0.629	neutral	N	0.39631603	None	None	N
R/V	0.8543	likely_pathogenic	0.7322	pathogenic	-0.312	Destabilizing	0.923	D	0.641	neutral	None	None	None	None	N
R/W	0.709	likely_pathogenic	0.5514	ambiguous	-0.363	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
R/Y	0.9185	likely_pathogenic	0.8333	pathogenic	-0.082	Destabilizing	0.987	D	0.699	prob.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.