TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5633	17122;17123;17124	chr2:178732072;178732071;178732070	chr2:179596799;179596798;179596797
N2AB	5316	16171;16172;16173	chr2:178732072;178732071;178732070	chr2:179596799;179596798;179596797
N2A	4389	13390;13391;13392	chr2:178732072;178732071;178732070	chr2:179596799;179596798;179596797
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-39
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.2065
• 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
V/I	None	None	0.997	N	0.734	0.318	0.644234019813	gnomAD-4.0.0	1.61996E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8948E-05	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
V/A	0.5142	ambiguous	0.5964	pathogenic	-2.068	Highly Destabilizing	0.999	D	0.778	deleterious	N	0.515531737	None	None	N
V/C	0.9001	likely_pathogenic	0.9247	pathogenic	-1.83	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/D	0.9805	likely_pathogenic	0.9886	pathogenic	-2.398	Highly Destabilizing	1.0	D	0.898	deleterious	D	0.546259745	None	None	N
V/E	0.9391	likely_pathogenic	0.9587	pathogenic	-2.26	Highly Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/F	0.6746	likely_pathogenic	0.7522	pathogenic	-1.354	Destabilizing	1.0	D	0.903	deleterious	D	0.545499277	None	None	N
V/G	0.7053	likely_pathogenic	0.7771	pathogenic	-2.496	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.546259745	None	None	N
V/H	0.9813	likely_pathogenic	0.9889	pathogenic	-2.033	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/I	0.0826	likely_benign	0.0859	benign	-0.91	Destabilizing	0.997	D	0.734	prob.delet.	N	0.512697341	None	None	N
V/K	0.9603	likely_pathogenic	0.9744	pathogenic	-1.66	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/L	0.4738	ambiguous	0.532	ambiguous	-0.91	Destabilizing	0.997	D	0.771	deleterious	N	0.517733783	None	None	N
V/M	0.4238	ambiguous	0.5147	ambiguous	-1.071	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/N	0.9182	likely_pathogenic	0.9479	pathogenic	-1.81	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/P	0.9209	likely_pathogenic	0.9472	pathogenic	-1.268	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/Q	0.9261	likely_pathogenic	0.9521	pathogenic	-1.807	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/R	0.9351	likely_pathogenic	0.9569	pathogenic	-1.337	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/S	0.7212	likely_pathogenic	0.7901	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/T	0.5773	likely_pathogenic	0.6436	pathogenic	-2.161	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
V/W	0.987	likely_pathogenic	0.9922	pathogenic	-1.68	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Y	0.9588	likely_pathogenic	0.9747	pathogenic	-1.365	Destabilizing	1.0	D	0.904	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.