TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32069	96430;96431;96432	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
N2AB	30428	91507;91508;91509	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
N2A	29501	88726;88727;88728	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
N2B	23004	69235;69236;69237	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
Novex-1	23129	69610;69611;69612	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
Novex-2	23196	69811;69812;69813	chr2:178543939;178543938;178543937	chr2:179408666;179408665;179408664
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-153
• Domain position: 53
• Structural Position: 137
• Q(SASA): 0.1941
• 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
L/F	rs1285541377	None	0.996	N	0.569	0.259	0.586419759405	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
L/F	rs1285541377	None	0.996	N	0.569	0.259	0.586419759405	gnomAD-4.0.0	1.8592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54298E-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
L/A	0.5389	ambiguous	0.503	ambiguous	-2.629	Highly Destabilizing	0.079	N	0.297	neutral	None	None	None	None	N
L/C	0.6442	likely_pathogenic	0.624	pathogenic	-1.765	Destabilizing	0.1	N	0.384	neutral	None	None	None	None	N
L/D	0.9646	likely_pathogenic	0.9567	pathogenic	-2.915	Highly Destabilizing	0.982	D	0.629	neutral	None	None	None	None	N
L/E	0.7795	likely_pathogenic	0.7467	pathogenic	-2.687	Highly Destabilizing	0.939	D	0.635	neutral	None	None	None	None	N
L/F	0.2566	likely_benign	0.2333	benign	-1.602	Destabilizing	0.996	D	0.569	neutral	N	0.501773845	None	None	N
L/G	0.8699	likely_pathogenic	0.8514	pathogenic	-3.174	Highly Destabilizing	0.939	D	0.579	neutral	None	None	None	None	N
L/H	0.504	ambiguous	0.4874	ambiguous	-2.65	Highly Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
L/I	0.1321	likely_benign	0.1307	benign	-1.049	Destabilizing	0.969	D	0.503	neutral	None	None	None	None	N
L/K	0.7146	likely_pathogenic	0.689	pathogenic	-1.965	Destabilizing	0.939	D	0.581	neutral	None	None	None	None	N
L/M	0.1182	likely_benign	0.116	benign	-0.932	Destabilizing	0.996	D	0.573	neutral	N	0.488652619	None	None	N
L/N	0.6965	likely_pathogenic	0.6847	pathogenic	-2.304	Highly Destabilizing	0.982	D	0.635	neutral	None	None	None	None	N
L/P	0.9892	likely_pathogenic	0.988	pathogenic	-1.558	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
L/Q	0.3714	ambiguous	0.348	ambiguous	-2.16	Highly Destabilizing	0.991	D	0.609	neutral	None	None	None	None	N
L/R	0.6008	likely_pathogenic	0.576	pathogenic	-1.68	Destabilizing	0.991	D	0.601	neutral	None	None	None	None	N
L/S	0.5313	ambiguous	0.4945	ambiguous	-2.991	Highly Destabilizing	0.159	N	0.361	neutral	N	0.389909777	None	None	N
L/T	0.3901	ambiguous	0.3555	ambiguous	-2.622	Highly Destabilizing	0.884	D	0.512	neutral	None	None	None	None	N
L/V	0.1364	likely_benign	0.133	benign	-1.558	Destabilizing	0.826	D	0.501	neutral	N	0.452038458	None	None	N
L/W	0.5847	likely_pathogenic	0.5628	ambiguous	-2.028	Highly Destabilizing	0.999	D	0.619	neutral	N	0.500126962	None	None	N
L/Y	0.5575	ambiguous	0.5345	ambiguous	-1.747	Destabilizing	0.997	D	0.593	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.