TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33231	99916;99917;99918	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
N2AB	31590	94993;94994;94995	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
N2A	30663	92212;92213;92214	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
N2B	24166	72721;72722;72723	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
Novex-1	24291	73096;73097;73098	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
Novex-2	24358	73297;73298;73299	chr2:178537516;178537515;178537514	chr2:179402243;179402242;179402241
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-157
• Domain position: 29
• Structural Position: 49
• Q(SASA): 0.11
• 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/L	None	None	0.959	N	0.497	0.336	0.366466682447	gnomAD-4.0.0	1.59138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.8814	likely_pathogenic	0.814	pathogenic	-2.873	Highly Destabilizing	0.993	D	0.655	neutral	None	None	None	None	N
F/C	0.5943	likely_pathogenic	0.5386	ambiguous	-1.551	Destabilizing	1.0	D	0.771	deleterious	N	0.504042493	None	None	N
F/D	0.9745	likely_pathogenic	0.9563	pathogenic	-2.418	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
F/E	0.9377	likely_pathogenic	0.8923	pathogenic	-2.275	Highly Destabilizing	0.997	D	0.791	deleterious	None	None	None	None	N
F/G	0.9488	likely_pathogenic	0.9216	pathogenic	-3.253	Highly Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
F/H	0.6071	likely_pathogenic	0.5287	ambiguous	-1.482	Destabilizing	0.994	D	0.772	deleterious	None	None	None	None	N
F/I	0.4963	ambiguous	0.4211	ambiguous	-1.663	Destabilizing	0.994	D	0.67	neutral	N	0.446802344	None	None	N
F/K	0.8726	likely_pathogenic	0.8204	pathogenic	-1.795	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
F/L	0.9175	likely_pathogenic	0.9021	pathogenic	-1.663	Destabilizing	0.959	D	0.497	neutral	N	0.400008474	None	None	N
F/M	0.7169	likely_pathogenic	0.6642	pathogenic	-1.264	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
F/N	0.8463	likely_pathogenic	0.7792	pathogenic	-1.993	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
F/P	0.9997	likely_pathogenic	0.9997	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
F/Q	0.8094	likely_pathogenic	0.7369	pathogenic	-2.081	Highly Destabilizing	0.997	D	0.803	deleterious	None	None	None	None	N
F/R	0.7779	likely_pathogenic	0.7156	pathogenic	-1.075	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
F/S	0.7261	likely_pathogenic	0.6125	pathogenic	-2.734	Highly Destabilizing	0.999	D	0.755	deleterious	N	0.426504429	None	None	N
F/T	0.785	likely_pathogenic	0.6968	pathogenic	-2.5	Highly Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
F/V	0.5381	ambiguous	0.4593	ambiguous	-2.071	Highly Destabilizing	0.972	D	0.632	neutral	N	0.473199511	None	None	N
F/W	0.6068	likely_pathogenic	0.5628	ambiguous	-0.54	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
F/Y	0.1672	likely_benign	0.153	benign	-0.872	Destabilizing	0.062	N	0.349	neutral	N	0.438449432	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.