TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22780	68563;68564;68565	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
N2AB	21139	63640;63641;63642	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
N2A	20212	60859;60860;60861	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
N2B	13715	41368;41369;41370	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
Novex-1	13840	41743;41744;41745	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
Novex-2	13907	41944;41945;41946	chr2:178578177;178578176;178578175	chr2:179442904;179442903;179442902
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-53
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0688
• 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/V	rs878857012	-1.947	None	N	0.249	0.034	None	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
L/V	rs878857012	-1.947	None	N	0.249	0.034	None	gnomAD-4.0.0	6.38943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.58752E-06	0	3.03067E-05

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	0.6384	likely_pathogenic	0.6562	pathogenic	-3.283	Highly Destabilizing	0.007	N	0.541	neutral	None	None	None	None	N
L/C	0.7737	likely_pathogenic	0.7418	pathogenic	-2.395	Highly Destabilizing	0.628	D	0.73	prob.delet.	None	None	None	None	N
L/D	0.9967	likely_pathogenic	0.9975	pathogenic	-3.841	Highly Destabilizing	0.356	N	0.754	deleterious	None	None	None	None	N
L/E	0.9794	likely_pathogenic	0.9836	pathogenic	-3.54	Highly Destabilizing	0.136	N	0.732	prob.delet.	None	None	None	None	N
L/F	0.6512	likely_pathogenic	0.6005	pathogenic	-2.002	Highly Destabilizing	0.055	N	0.535	neutral	D	0.523789581	None	None	N
L/G	0.9515	likely_pathogenic	0.9505	pathogenic	-3.823	Highly Destabilizing	0.136	N	0.695	prob.neutral	None	None	None	None	N
L/H	0.9754	likely_pathogenic	0.9772	pathogenic	-3.297	Highly Destabilizing	0.828	D	0.812	deleterious	D	0.52404307	None	None	N
L/I	0.0557	likely_benign	0.0591	benign	-1.618	Destabilizing	None	N	0.239	neutral	N	0.409865683	None	None	N
L/K	0.9795	likely_pathogenic	0.9843	pathogenic	-2.718	Highly Destabilizing	0.136	N	0.685	prob.neutral	None	None	None	None	N
L/M	0.1819	likely_benign	0.1675	benign	-1.794	Destabilizing	0.214	N	0.549	neutral	None	None	None	None	N
L/N	0.9729	likely_pathogenic	0.9768	pathogenic	-3.432	Highly Destabilizing	0.628	D	0.788	deleterious	None	None	None	None	N
L/P	0.9694	likely_pathogenic	0.9724	pathogenic	-2.171	Highly Destabilizing	0.56	D	0.764	deleterious	N	0.50133046	None	None	N
L/Q	0.9505	likely_pathogenic	0.9541	pathogenic	-3.108	Highly Destabilizing	0.628	D	0.781	deleterious	None	None	None	None	N
L/R	0.963	likely_pathogenic	0.9697	pathogenic	-2.625	Highly Destabilizing	0.295	N	0.767	deleterious	D	0.52404307	None	None	N
L/S	0.9277	likely_pathogenic	0.9331	pathogenic	-3.9	Highly Destabilizing	0.136	N	0.633	neutral	None	None	None	None	N
L/T	0.6249	likely_pathogenic	0.6524	pathogenic	-3.457	Highly Destabilizing	0.031	N	0.543	neutral	None	None	None	None	N
L/V	0.0675	likely_benign	0.0651	benign	-2.171	Highly Destabilizing	None	N	0.249	neutral	N	0.402491419	None	None	N
L/W	0.9623	likely_pathogenic	0.9615	pathogenic	-2.267	Highly Destabilizing	0.864	D	0.796	deleterious	None	None	None	None	N
L/Y	0.9611	likely_pathogenic	0.9585	pathogenic	-2.247	Highly Destabilizing	0.356	N	0.655	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.