TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16591	49996;49997;49998	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
N2AB	14950	45073;45074;45075	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
N2A	14023	42292;42293;42294	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
N2B	7526	22801;22802;22803	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
Novex-1	7651	23176;23177;23178	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
Novex-2	7718	23377;23378;23379	chr2:178612950;178612949;178612948	chr2:179477677;179477676;179477675
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-8
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.192
• 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/R	None	None	0.999	N	0.87	0.312	0.719045985532	gnomAD-4.0.0	1.59354E-06	None	None	None	None	N	None	0	0	None	0	2.78956E-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
L/A	0.4027	ambiguous	0.4443	ambiguous	-2.116	Highly Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N
L/C	0.5133	ambiguous	0.5046	ambiguous	-1.377	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9391	likely_pathogenic	0.958	pathogenic	-2.459	Highly Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
L/E	0.4693	ambiguous	0.5392	ambiguous	-2.236	Highly Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
L/F	0.2914	likely_benign	0.306	benign	-1.227	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/G	0.7478	likely_pathogenic	0.7895	pathogenic	-2.635	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/H	0.3542	ambiguous	0.3963	ambiguous	-2.279	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/I	0.1983	likely_benign	0.2233	benign	-0.619	Destabilizing	1.0	D	0.489	neutral	None	None	None	None	N
L/K	0.1928	likely_benign	0.2243	benign	-1.263	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
L/M	0.1143	likely_benign	0.1127	benign	-0.719	Destabilizing	1.0	D	0.758	deleterious	N	0.470713443	None	None	N
L/N	0.6654	likely_pathogenic	0.7036	pathogenic	-1.607	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
L/P	0.9882	likely_pathogenic	0.9918	pathogenic	-1.1	Destabilizing	1.0	D	0.893	deleterious	N	0.472693421	None	None	N
L/Q	0.0944	likely_benign	0.103	benign	-1.449	Destabilizing	0.981	D	0.413	neutral	N	0.368394292	None	None	N
L/R	0.1619	likely_benign	0.1963	benign	-1.176	Destabilizing	0.999	D	0.87	deleterious	N	0.333479874	None	None	N
L/S	0.5387	ambiguous	0.59	pathogenic	-2.252	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/T	0.4788	ambiguous	0.534	ambiguous	-1.891	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/V	0.1884	likely_benign	0.2058	benign	-1.1	Destabilizing	0.998	D	0.475	neutral	N	0.473894694	None	None	N
L/W	0.4519	ambiguous	0.5032	ambiguous	-1.664	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/Y	0.516	ambiguous	0.5247	ambiguous	-1.323	Destabilizing	1.0	D	0.884	deleterious	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.