TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35475	106648;106649;106650	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
N2AB	33834	101725;101726;101727	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
N2A	32907	98944;98945;98946	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
N2B	26410	79453;79454;79455	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
Novex-1	26535	79828;79829;79830	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
Novex-2	26602	80029;80030;80031	chr2:178530068;178530067;178530066	chr2:179394795;179394794;179394793
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-166
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0832
• 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
F/C	None	None	0.977	N	0.649	0.178	0.481246930725	gnomAD-4.0.0	1.20035E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	0	0
F/I	rs377463445	-1.712	0.802	N	0.565	0.146	0.271763555656	gnomAD-2.1.1	1.54253E-04	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	1.24211E-03	None	0	0	0
F/I	rs377463445	-1.712	0.802	N	0.565	0.146	0.271763555656	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	1.65906E-03	0
F/I	rs377463445	-1.712	0.802	N	0.565	0.146	0.271763555656	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
F/I	rs377463445	-1.712	0.802	N	0.565	0.146	0.271763555656	gnomAD-4.0.0	7.8827E-05	None	None	None	None	N	None	0	0	None	0	2.23424E-05	None	0	0	0	1.36515E-03	4.80754E-05
F/L	rs1445321656	-1.712	0.451	N	0.473	0.155	0.187945064343	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
F/L	rs1445321656	-1.712	0.451	N	0.473	0.155	0.187945064343	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
F/L	rs1445321656	-1.712	0.451	N	0.473	0.155	0.187945064343	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46977E-05	0	0
F/V	rs377463445	-2.184	0.451	N	0.569	0.161	0.33835085245	gnomAD-2.1.1	8.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
F/V	rs377463445	-2.184	0.451	N	0.569	0.161	0.33835085245	gnomAD-4.0.0	6.16861E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19958E-06	0	1.65876E-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
F/A	0.6486	likely_pathogenic	0.6431	pathogenic	-2.555	Highly Destabilizing	0.005	N	0.57	neutral	None	None	None	None	N
F/C	0.3696	ambiguous	0.346	ambiguous	-1.287	Destabilizing	0.977	D	0.649	neutral	N	0.372784588	None	None	N
F/D	0.8735	likely_pathogenic	0.8795	pathogenic	-2.337	Highly Destabilizing	0.843	D	0.659	neutral	None	None	None	None	N
F/E	0.9231	likely_pathogenic	0.924	pathogenic	-2.157	Highly Destabilizing	0.522	D	0.636	neutral	None	None	None	None	N
F/G	0.8354	likely_pathogenic	0.8333	pathogenic	-2.958	Highly Destabilizing	0.353	N	0.651	neutral	None	None	None	None	N
F/H	0.6567	likely_pathogenic	0.6501	pathogenic	-1.388	Destabilizing	0.983	D	0.609	neutral	None	None	None	None	N
F/I	0.1729	likely_benign	0.1643	benign	-1.261	Destabilizing	0.802	D	0.565	neutral	N	0.443548608	None	None	N
F/K	0.9157	likely_pathogenic	0.9212	pathogenic	-1.402	Destabilizing	0.015	N	0.649	neutral	None	None	None	None	N
F/L	0.7685	likely_pathogenic	0.7674	pathogenic	-1.261	Destabilizing	0.451	N	0.473	neutral	N	0.440257587	None	None	N
F/M	0.5505	ambiguous	0.5487	ambiguous	-0.996	Destabilizing	0.983	D	0.604	neutral	None	None	None	None	N
F/N	0.6768	likely_pathogenic	0.6804	pathogenic	-1.706	Destabilizing	0.843	D	0.673	neutral	None	None	None	None	N
F/P	0.9883	likely_pathogenic	0.9885	pathogenic	-1.699	Destabilizing	0.843	D	0.676	prob.neutral	None	None	None	None	N
F/Q	0.8724	likely_pathogenic	0.8725	pathogenic	-1.712	Destabilizing	0.726	D	0.686	prob.neutral	None	None	None	None	N
F/R	0.8346	likely_pathogenic	0.8418	pathogenic	-0.939	Destabilizing	0.57	D	0.667	neutral	None	None	None	None	N
F/S	0.5314	ambiguous	0.531	ambiguous	-2.407	Highly Destabilizing	0.292	N	0.646	neutral	N	0.376630182	None	None	N
F/T	0.6183	likely_pathogenic	0.6142	pathogenic	-2.129	Highly Destabilizing	0.522	D	0.628	neutral	None	None	None	None	N
F/V	0.2133	likely_benign	0.2011	benign	-1.699	Destabilizing	0.451	N	0.569	neutral	N	0.442681816	None	None	N
F/W	0.5313	ambiguous	0.5478	ambiguous	-0.145	Destabilizing	0.995	D	0.621	neutral	None	None	None	None	N
F/Y	0.1248	likely_benign	0.1176	benign	-0.488	Destabilizing	0.925	D	0.585	neutral	N	0.410166753	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.