TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7816	23671;23672;23673	chr2:178720196;178720195;178720194	chr2:179584923;179584922;179584921
N2AB	7499	22720;22721;22722	chr2:178720196;178720195;178720194	chr2:179584923;179584922;179584921
N2A	6572	19939;19940;19941	chr2:178720196;178720195;178720194	chr2:179584923;179584922;179584921
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-63
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.1156
• 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
A/V	None	None	0.997	N	0.719	0.253	0.215109475489	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-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
A/C	0.6304	likely_pathogenic	0.6216	pathogenic	-0.928	Destabilizing	0.468	N	0.448	neutral	None	None	None	None	N
A/D	0.9786	likely_pathogenic	0.9737	pathogenic	-2.578	Highly Destabilizing	0.998	D	0.844	deleterious	N	0.487585438	None	None	N
A/E	0.9731	likely_pathogenic	0.9677	pathogenic	-2.331	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/F	0.9066	likely_pathogenic	0.8857	pathogenic	-0.648	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/G	0.2276	likely_benign	0.2611	benign	-1.652	Destabilizing	0.025	N	0.429	neutral	N	0.494401503	None	None	N
A/H	0.9886	likely_pathogenic	0.9847	pathogenic	-2.175	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/I	0.6699	likely_pathogenic	0.6215	pathogenic	0.265	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/K	0.9959	likely_pathogenic	0.9942	pathogenic	-1.229	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/L	0.5958	likely_pathogenic	0.5738	pathogenic	0.265	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
A/M	0.6462	likely_pathogenic	0.617	pathogenic	0.058	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/N	0.9333	likely_pathogenic	0.9186	pathogenic	-1.647	Destabilizing	0.989	D	0.844	deleterious	None	None	None	None	N
A/P	0.9881	likely_pathogenic	0.9838	pathogenic	-0.163	Destabilizing	0.999	D	0.787	deleterious	N	0.487585438	None	None	N
A/Q	0.9725	likely_pathogenic	0.9654	pathogenic	-1.372	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
A/R	0.9901	likely_pathogenic	0.9862	pathogenic	-1.399	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/S	0.2214	likely_benign	0.2108	benign	-2.016	Highly Destabilizing	0.859	D	0.693	prob.neutral	N	0.452844958	None	None	N
A/T	0.2228	likely_benign	0.1915	benign	-1.645	Destabilizing	0.991	D	0.719	prob.delet.	N	0.486512738	None	None	N
A/V	0.3075	likely_benign	0.2627	benign	-0.163	Destabilizing	0.997	D	0.719	prob.delet.	N	0.482045494	None	None	N
A/W	0.9947	likely_pathogenic	0.9929	pathogenic	-1.549	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/Y	0.9736	likely_pathogenic	0.9644	pathogenic	-0.954	Destabilizing	1.0	D	0.862	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.