TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7855	23788;23789;23790	chr2:178720079;178720078;178720077	chr2:179584806;179584805;179584804
N2AB	7538	22837;22838;22839	chr2:178720079;178720078;178720077	chr2:179584806;179584805;179584804
N2A	6611	20056;20057;20058	chr2:178720079;178720078;178720077	chr2:179584806;179584805;179584804
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-63
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.2047
• 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	rs1364646771	-1.444	0.001	N	0.279	0.096	0.260249123532	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
L/V	rs1364646771	-1.444	0.001	N	0.279	0.096	0.260249123532	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
L/V	rs1364646771	-1.444	0.001	N	0.279	0.096	0.260249123532	gnomAD-4.0.0	2.56253E-06	None	None	None	None	N	None	0	1.69503E-05	None	0	0	None	0	0	0	0	2.84527E-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	0.5357	ambiguous	0.4795	ambiguous	-2.631	Highly Destabilizing	0.116	N	0.643	neutral	None	None	None	None	N
L/C	0.6687	likely_pathogenic	0.6059	pathogenic	-2.184	Highly Destabilizing	0.944	D	0.753	deleterious	None	None	None	None	N
L/D	0.939	likely_pathogenic	0.9218	pathogenic	-2.761	Highly Destabilizing	0.818	D	0.832	deleterious	None	None	None	None	N
L/E	0.7911	likely_pathogenic	0.7442	pathogenic	-2.624	Highly Destabilizing	0.818	D	0.811	deleterious	None	None	None	None	N
L/F	0.1148	likely_benign	0.0874	benign	-1.767	Destabilizing	0.002	N	0.396	neutral	None	None	None	None	N
L/G	0.86	likely_pathogenic	0.8197	pathogenic	-3.116	Highly Destabilizing	0.818	D	0.813	deleterious	None	None	None	None	N
L/H	0.5505	ambiguous	0.4869	ambiguous	-2.413	Highly Destabilizing	0.981	D	0.828	deleterious	None	None	None	None	N
L/I	0.0785	likely_benign	0.0757	benign	-1.267	Destabilizing	None	N	0.265	neutral	None	None	None	None	N
L/K	0.7601	likely_pathogenic	0.7047	pathogenic	-2.124	Highly Destabilizing	0.818	D	0.799	deleterious	None	None	None	None	N
L/M	0.1319	likely_benign	0.1187	benign	-1.19	Destabilizing	0.627	D	0.631	neutral	N	0.504534734	None	None	N
L/N	0.8224	likely_pathogenic	0.7667	pathogenic	-2.259	Highly Destabilizing	0.932	D	0.834	deleterious	None	None	None	None	N
L/P	0.8894	likely_pathogenic	0.8758	pathogenic	-1.698	Destabilizing	0.912	D	0.837	deleterious	D	0.533060697	None	None	N
L/Q	0.5291	ambiguous	0.4804	ambiguous	-2.283	Highly Destabilizing	0.912	D	0.811	deleterious	D	0.533060697	None	None	N
L/R	0.6263	likely_pathogenic	0.5779	pathogenic	-1.598	Destabilizing	0.773	D	0.819	deleterious	D	0.533060697	None	None	N
L/S	0.7281	likely_pathogenic	0.6683	pathogenic	-2.976	Highly Destabilizing	0.388	N	0.775	deleterious	None	None	None	None	N
L/T	0.5127	ambiguous	0.466	ambiguous	-2.698	Highly Destabilizing	0.388	N	0.677	prob.neutral	None	None	None	None	N
L/V	0.1172	likely_benign	0.1116	benign	-1.698	Destabilizing	0.001	N	0.279	neutral	N	0.484169519	None	None	N
L/W	0.3365	likely_benign	0.287	benign	-2.017	Highly Destabilizing	0.981	D	0.797	deleterious	None	None	None	None	N
L/Y	0.4931	ambiguous	0.4058	ambiguous	-1.793	Destabilizing	0.527	D	0.753	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.