TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13986	42181;42182;42183	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
N2AB	12345	37258;37259;37260	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
N2A	11418	34477;34478;34479	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
N2B	4921	14986;14987;14988	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
Novex-1	5046	15361;15362;15363	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
Novex-2	5113	15562;15563;15564	chr2:178635233;178635232;178635231	chr2:179499960;179499959;179499958
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-90
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1547
• 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
A/G	None	None	0.361	N	0.655	0.138	0.101711395817	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43324E-05	0
A/T	rs1208784748	None	0.001	N	0.249	0.198	0.0611884634855	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
A/C	0.5016	ambiguous	0.328	benign	-1.105	Destabilizing	0.005	N	0.489	neutral	None	None	None	None	N
A/D	0.9938	likely_pathogenic	0.9869	pathogenic	-2.571	Highly Destabilizing	0.428	N	0.739	deleterious	None	None	None	None	N
A/E	0.9887	likely_pathogenic	0.978	pathogenic	-2.289	Highly Destabilizing	0.361	N	0.793	deleterious	N	0.439508754	None	None	N
A/F	0.973	likely_pathogenic	0.9423	pathogenic	-0.748	Destabilizing	0.842	D	0.787	deleterious	None	None	None	None	N
A/G	0.556	ambiguous	0.4395	ambiguous	-2.005	Highly Destabilizing	0.361	N	0.655	prob.neutral	N	0.439092943	None	None	N
A/H	0.9938	likely_pathogenic	0.9868	pathogenic	-2.316	Highly Destabilizing	0.984	D	0.749	deleterious	None	None	None	None	N
A/I	0.8465	likely_pathogenic	0.6664	pathogenic	-0.112	Destabilizing	0.272	N	0.801	deleterious	None	None	None	None	N
A/K	0.9979	likely_pathogenic	0.9957	pathogenic	-1.226	Destabilizing	0.428	N	0.785	deleterious	None	None	None	None	N
A/L	0.7534	likely_pathogenic	0.5926	pathogenic	-0.112	Destabilizing	0.134	N	0.672	prob.neutral	None	None	None	None	N
A/M	0.8355	likely_pathogenic	0.6802	pathogenic	-0.558	Destabilizing	0.842	D	0.763	deleterious	None	None	None	None	N
A/N	0.9793	likely_pathogenic	0.9485	pathogenic	-1.801	Destabilizing	0.724	D	0.763	deleterious	None	None	None	None	N
A/P	0.9975	likely_pathogenic	0.9946	pathogenic	-0.55	Destabilizing	0.8	D	0.803	deleterious	N	0.439092943	None	None	N
A/Q	0.9849	likely_pathogenic	0.9698	pathogenic	-1.42	Destabilizing	0.842	D	0.804	deleterious	None	None	None	None	N
A/R	0.9924	likely_pathogenic	0.9863	pathogenic	-1.537	Destabilizing	0.842	D	0.801	deleterious	None	None	None	None	N
A/S	0.3968	ambiguous	0.2551	benign	-2.104	Highly Destabilizing	0.104	N	0.594	neutral	N	0.438880823	None	None	N
A/T	0.3443	ambiguous	0.163	benign	-1.701	Destabilizing	0.001	N	0.249	neutral	N	0.339582731	None	None	N
A/V	0.499	ambiguous	0.2786	benign	-0.55	Destabilizing	0.008	N	0.307	neutral	N	0.403615201	None	None	N
A/W	0.9982	likely_pathogenic	0.9952	pathogenic	-1.457	Destabilizing	0.984	D	0.805	deleterious	None	None	None	None	N
A/Y	0.9913	likely_pathogenic	0.9808	pathogenic	-1.077	Destabilizing	0.942	D	0.787	deleterious	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.