TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7643	23152;23153;23154	chr2:178721092;178721091;178721090	chr2:179585819;179585818;179585817
N2AB	7326	22201;22202;22203	chr2:178721092;178721091;178721090	chr2:179585819;179585818;179585817
N2A	6399	19420;19421;19422	chr2:178721092;178721091;178721090	chr2:179585819;179585818;179585817
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-61
• Domain position: 36
• Structural Position: 49
• Q(SASA): 0.1618
• 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	rs1236884479	None	0.999	N	0.724	0.394	0.692523172946	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/C	rs1236884479	None	0.999	N	0.724	0.394	0.692523172946	gnomAD-4.0.0	6.5716E-06	None	None	None	None	N	None	2.41266E-05	0	None	0	0	None	0	0	0	0	0
F/L	rs1220233806	-1.726	0.885	N	0.487	0.253	0.502379540653	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
F/L	rs1220233806	-1.726	0.885	N	0.487	0.253	0.502379540653	gnomAD-4.0.0	1.59267E-06	None	None	None	None	N	None	0	0	None	0	2.77316E-05	None	0	0	0	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
F/A	0.907	likely_pathogenic	0.9627	pathogenic	-2.693	Highly Destabilizing	0.953	D	0.623	neutral	None	None	None	None	N
F/C	0.7146	likely_pathogenic	0.816	pathogenic	-1.63	Destabilizing	0.999	D	0.724	prob.delet.	N	0.504755094	None	None	N
F/D	0.957	likely_pathogenic	0.9855	pathogenic	-2.012	Highly Destabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
F/E	0.9474	likely_pathogenic	0.9813	pathogenic	-1.898	Destabilizing	0.993	D	0.745	deleterious	None	None	None	None	N
F/G	0.9355	likely_pathogenic	0.9745	pathogenic	-3.046	Highly Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
F/H	0.5881	likely_pathogenic	0.743	pathogenic	-1.302	Destabilizing	0.986	D	0.704	prob.neutral	None	None	None	None	N
F/I	0.5421	ambiguous	0.7298	pathogenic	-1.593	Destabilizing	0.982	D	0.6	neutral	N	0.457226278	None	None	N
F/K	0.8555	likely_pathogenic	0.9486	pathogenic	-1.47	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	N
F/L	0.9212	likely_pathogenic	0.9633	pathogenic	-1.593	Destabilizing	0.885	D	0.487	neutral	N	0.470311135	None	None	N
F/M	0.7601	likely_pathogenic	0.8598	pathogenic	-1.381	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
F/N	0.8231	likely_pathogenic	0.9187	pathogenic	-1.553	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
F/P	0.9994	likely_pathogenic	0.9998	pathogenic	-1.96	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
F/Q	0.8529	likely_pathogenic	0.9367	pathogenic	-1.699	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
F/R	0.7555	likely_pathogenic	0.8886	pathogenic	-0.765	Destabilizing	0.993	D	0.77	deleterious	None	None	None	None	N
F/S	0.7635	likely_pathogenic	0.8968	pathogenic	-2.355	Highly Destabilizing	0.991	D	0.706	prob.neutral	N	0.47795197	None	None	N
F/T	0.8555	likely_pathogenic	0.9444	pathogenic	-2.149	Highly Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
F/V	0.5742	likely_pathogenic	0.7533	pathogenic	-1.96	Destabilizing	0.939	D	0.581	neutral	N	0.455415852	None	None	N
F/W	0.4698	ambiguous	0.6054	pathogenic	-0.515	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
F/Y	0.1008	likely_benign	0.1225	benign	-0.771	Destabilizing	0.02	N	0.244	neutral	N	0.39669881	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.