TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25349	76270;76271;76272	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
N2AB	23708	71347;71348;71349	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
N2A	22781	68566;68567;68568	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
N2B	16284	49075;49076;49077	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
Novex-1	16409	49450;49451;49452	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
Novex-2	16476	49651;49652;49653	chr2:178570087;178570086;178570085	chr2:179434814;179434813;179434812
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-72
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9785
• 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
I/V	None	None	0.012	N	0.167	0.06	0.317667799068	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.4655	ambiguous	0.468	ambiguous	-0.452	Destabilizing	0.373	N	0.269	neutral	None	None	None	None	N
I/C	0.6895	likely_pathogenic	0.6823	pathogenic	-0.853	Destabilizing	0.996	D	0.194	neutral	None	None	None	None	N
I/D	0.8308	likely_pathogenic	0.8236	pathogenic	-0.154	Destabilizing	0.91	D	0.229	neutral	None	None	None	None	N
I/E	0.7415	likely_pathogenic	0.7231	pathogenic	-0.245	Destabilizing	0.59	D	0.221	neutral	None	None	None	None	N
I/F	0.1935	likely_benign	0.1858	benign	-0.642	Destabilizing	0.884	D	0.199	neutral	N	0.514035774	None	None	N
I/G	0.6457	likely_pathogenic	0.6512	pathogenic	-0.534	Destabilizing	0.742	D	0.251	neutral	None	None	None	None	N
I/H	0.642	likely_pathogenic	0.6146	pathogenic	0.053	Stabilizing	0.987	D	0.185	neutral	None	None	None	None	N
I/K	0.5723	likely_pathogenic	0.52	ambiguous	-0.342	Destabilizing	0.009	N	0.226	neutral	None	None	None	None	N
I/L	0.1062	likely_benign	0.1064	benign	-0.355	Destabilizing	0.003	N	0.146	neutral	N	0.404886724	None	None	N
I/M	0.1172	likely_benign	0.1167	benign	-0.649	Destabilizing	0.884	D	0.211	neutral	N	0.442674321	None	None	N
I/N	0.3557	ambiguous	0.3448	ambiguous	-0.217	Destabilizing	0.884	D	0.211	neutral	N	0.433494691	None	None	N
I/P	0.6972	likely_pathogenic	0.718	pathogenic	-0.361	Destabilizing	0.953	D	0.212	neutral	None	None	None	None	N
I/Q	0.562	ambiguous	0.5347	ambiguous	-0.374	Destabilizing	0.91	D	0.209	neutral	None	None	None	None	N
I/R	0.5041	ambiguous	0.4427	ambiguous	0.073	Stabilizing	0.835	D	0.229	neutral	None	None	None	None	N
I/S	0.3893	ambiguous	0.3909	ambiguous	-0.606	Destabilizing	0.684	D	0.251	neutral	N	0.41146598	None	None	N
I/T	0.3629	ambiguous	0.3611	ambiguous	-0.599	Destabilizing	0.684	D	0.233	neutral	N	0.410119186	None	None	N
I/V	0.0813	likely_benign	0.0811	benign	-0.361	Destabilizing	0.012	N	0.167	neutral	N	0.415122361	None	None	N
I/W	0.7944	likely_pathogenic	0.7698	pathogenic	-0.658	Destabilizing	0.996	D	0.239	neutral	None	None	None	None	N
I/Y	0.5748	likely_pathogenic	0.5544	ambiguous	-0.433	Destabilizing	0.984	D	0.207	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.