TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13690	41293;41294;41295	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
N2AB	12049	36370;36371;36372	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
N2A	11122	33589;33590;33591	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
N2B	4625	14098;14099;14100	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
Novex-1	4750	14473;14474;14475	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
Novex-2	4817	14674;14675;14676	chr2:178636659;178636658;178636657	chr2:179501386;179501385;179501384
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-87
• Domain position: 7
• Structural Position: 9
• Q(SASA): 0.4945
• 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
K/R	None	None	0.124	N	0.531	0.198	0.295974979623	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31879E-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
K/A	0.6991	likely_pathogenic	0.7754	pathogenic	-0.118	Destabilizing	0.157	N	0.603	neutral	None	None	None	None	N
K/C	0.9572	likely_pathogenic	0.9615	pathogenic	-0.403	Destabilizing	0.968	D	0.797	deleterious	None	None	None	None	N
K/D	0.8475	likely_pathogenic	0.9088	pathogenic	0.03	Stabilizing	0.272	N	0.586	neutral	None	None	None	None	N
K/E	0.2969	likely_benign	0.4158	ambiguous	0.081	Stabilizing	0.055	N	0.506	neutral	N	0.422408108	None	None	N
K/F	0.991	likely_pathogenic	0.9928	pathogenic	-0.104	Destabilizing	0.89	D	0.775	deleterious	None	None	None	None	N
K/G	0.75	likely_pathogenic	0.8217	pathogenic	-0.378	Destabilizing	0.272	N	0.611	neutral	None	None	None	None	N
K/H	0.5995	likely_pathogenic	0.653	pathogenic	-0.572	Destabilizing	0.567	D	0.653	neutral	None	None	None	None	N
K/I	0.9005	likely_pathogenic	0.9164	pathogenic	0.505	Stabilizing	0.667	D	0.769	deleterious	N	0.519528412	None	None	N
K/L	0.8836	likely_pathogenic	0.9104	pathogenic	0.505	Stabilizing	0.272	N	0.611	neutral	None	None	None	None	N
K/M	0.7809	likely_pathogenic	0.8215	pathogenic	0.121	Stabilizing	0.726	D	0.653	neutral	None	None	None	None	N
K/N	0.712	likely_pathogenic	0.7844	pathogenic	-0.084	Destabilizing	0.22	N	0.545	neutral	N	0.51350282	None	None	N
K/P	0.9427	likely_pathogenic	0.9656	pathogenic	0.327	Stabilizing	0.726	D	0.641	neutral	None	None	None	None	N
K/Q	0.166	likely_benign	0.2116	benign	-0.175	Destabilizing	None	N	0.208	neutral	N	0.387677985	None	None	N
K/R	0.1356	likely_benign	0.1331	benign	-0.207	Destabilizing	0.124	N	0.531	neutral	N	0.478831435	None	None	N
K/S	0.6601	likely_pathogenic	0.7555	pathogenic	-0.584	Destabilizing	0.157	N	0.562	neutral	None	None	None	None	N
K/T	0.3519	ambiguous	0.4503	ambiguous	-0.362	Destabilizing	0.22	N	0.589	neutral	N	0.480571766	None	None	N
K/V	0.8317	likely_pathogenic	0.8589	pathogenic	0.327	Stabilizing	0.567	D	0.659	neutral	None	None	None	None	N
K/W	0.9843	likely_pathogenic	0.9877	pathogenic	-0.096	Destabilizing	0.968	D	0.816	deleterious	None	None	None	None	N
K/Y	0.9684	likely_pathogenic	0.9762	pathogenic	0.227	Stabilizing	0.726	D	0.747	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.