TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22829	68710;68711;68712	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
N2AB	21188	63787;63788;63789	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
N2A	20261	61006;61007;61008	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
N2B	13764	41515;41516;41517	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
Novex-1	13889	41890;41891;41892	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
Novex-2	13956	42091;42092;42093	chr2:178578030;178578029;178578028	chr2:179442757;179442756;179442755
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: Fn3-53
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3511
• 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/Q	rs747495409	-1.027	1.0	N	0.777	0.452	0.427254322456	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
P/Q	rs747495409	-1.027	1.0	N	0.777	0.452	0.427254322456	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
P/Q	rs747495409	-1.027	1.0	N	0.777	0.452	0.427254322456	gnomAD-4.0.0	1.97272E-05	None	None	None	None	I	None	7.24113E-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
P/A	0.1065	likely_benign	0.1015	benign	-1.348	Destabilizing	0.767	D	0.356	neutral	N	0.474669309	None	None	I
P/C	0.6039	likely_pathogenic	0.6035	pathogenic	-0.726	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/D	0.9468	likely_pathogenic	0.9575	pathogenic	-1.28	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
P/E	0.8431	likely_pathogenic	0.8655	pathogenic	-1.357	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/F	0.7279	likely_pathogenic	0.7469	pathogenic	-1.297	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/G	0.6314	likely_pathogenic	0.6445	pathogenic	-1.577	Destabilizing	0.997	D	0.62	neutral	None	None	None	None	I
P/H	0.6182	likely_pathogenic	0.6615	pathogenic	-1.092	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/I	0.6151	likely_pathogenic	0.6223	pathogenic	-0.846	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
P/K	0.899	likely_pathogenic	0.9178	pathogenic	-1.058	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/L	0.3855	ambiguous	0.399	ambiguous	-0.846	Destabilizing	0.999	D	0.708	prob.delet.	N	0.502066658	None	None	I
P/M	0.5773	likely_pathogenic	0.5903	pathogenic	-0.507	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/N	0.8236	likely_pathogenic	0.8384	pathogenic	-0.701	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/Q	0.6053	likely_pathogenic	0.6169	pathogenic	-1.006	Destabilizing	1.0	D	0.777	deleterious	N	0.504094574	None	None	I
P/R	0.7829	likely_pathogenic	0.8193	pathogenic	-0.408	Destabilizing	0.999	D	0.751	deleterious	N	0.488610439	None	None	I
P/S	0.3514	ambiguous	0.3534	ambiguous	-1.107	Destabilizing	0.992	D	0.609	neutral	N	0.475924234	None	None	I
P/T	0.3465	ambiguous	0.375	ambiguous	-1.095	Destabilizing	0.999	D	0.708	prob.delet.	N	0.497257719	None	None	I
P/V	0.3965	ambiguous	0.4011	ambiguous	-0.979	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
P/W	0.8921	likely_pathogenic	0.9012	pathogenic	-1.38	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/Y	0.7368	likely_pathogenic	0.7709	pathogenic	-1.133	Destabilizing	1.0	D	0.775	deleterious	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.