TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17643	53152;53153;53154	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
N2AB	16002	48229;48230;48231	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
N2A	15075	45448;45449;45450	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
N2B	8578	25957;25958;25959	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
Novex-1	8703	26332;26333;26334	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
Novex-2	8770	26533;26534;26535	chr2:178607860;178607859;178607858	chr2:179472587;179472586;179472585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-16
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1719
• 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
R/L	rs571636340	None	1.0	N	0.735	0.506	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs571636340	None	1.0	N	0.735	0.506	None	gnomAD-4.0.0	6.58146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47236E-05	0	0
R/Q	rs571636340	-0.978	1.0	N	0.79	0.395	0.356072328145	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
R/Q	rs571636340	-0.978	1.0	N	0.79	0.395	0.356072328145	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	1.94553E-04	None	0	0	1.47E-05	0	0
R/Q	rs571636340	-0.978	1.0	N	0.79	0.395	0.356072328145	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
R/Q	rs571636340	-0.978	1.0	N	0.79	0.395	0.356072328145	gnomAD-4.0.0	5.57973E-06	None	None	None	None	N	None	0	0	None	0	4.47668E-05	None	0	0	5.08767E-06	1.09827E-05	0
R/W	rs375944265	-0.601	1.0	D	0.757	0.453	None	gnomAD-2.1.1	7.51E-05	None	None	None	None	N	None	7.03002E-04	2.83E-05	None	0	5.18E-05	None	3.27E-05	None	0	7.82E-06	0
R/W	rs375944265	-0.601	1.0	D	0.757	0.453	None	gnomAD-3.1.2	2.96084E-04	None	None	None	None	N	None	7.72201E-04	4.59318E-04	0	0	5.83431E-04	None	0	0	2.94E-05	0	4.78011E-04
R/W	rs375944265	-0.601	1.0	D	0.757	0.453	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
R/W	rs375944265	-0.601	1.0	D	0.757	0.453	None	gnomAD-4.0.0	5.33156E-05	None	None	None	None	N	None	6.13481E-04	1.501E-04	None	0	6.71291E-05	None	0	0	1.86548E-05	1.09808E-05	8.00769E-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
R/A	0.8714	likely_pathogenic	0.8743	pathogenic	-1.553	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
R/C	0.3177	likely_benign	0.3364	benign	-1.595	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
R/D	0.9876	likely_pathogenic	0.9891	pathogenic	-0.829	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
R/E	0.8613	likely_pathogenic	0.8687	pathogenic	-0.639	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
R/F	0.8998	likely_pathogenic	0.9109	pathogenic	-0.942	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
R/G	0.8622	likely_pathogenic	0.8693	pathogenic	-1.891	Destabilizing	1.0	D	0.735	prob.delet.	D	0.538842416	None	None	N
R/H	0.2133	likely_benign	0.2376	benign	-1.858	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
R/I	0.7436	likely_pathogenic	0.7568	pathogenic	-0.594	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
R/K	0.2738	likely_benign	0.2681	benign	-1.254	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
R/L	0.6872	likely_pathogenic	0.7122	pathogenic	-0.594	Destabilizing	1.0	D	0.735	prob.delet.	N	0.509635345	None	None	N
R/M	0.7372	likely_pathogenic	0.7513	pathogenic	-1.056	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
R/N	0.9467	likely_pathogenic	0.9529	pathogenic	-1.111	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
R/P	0.9965	likely_pathogenic	0.997	pathogenic	-0.9	Destabilizing	1.0	D	0.783	deleterious	D	0.539349395	None	None	N
R/Q	0.2139	likely_benign	0.2164	benign	-1.026	Destabilizing	1.0	D	0.79	deleterious	N	0.482501735	None	None	N
R/S	0.9146	likely_pathogenic	0.9206	pathogenic	-1.912	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
R/T	0.8197	likely_pathogenic	0.832	pathogenic	-1.522	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/V	0.788	likely_pathogenic	0.7959	pathogenic	-0.9	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
R/W	0.4651	ambiguous	0.4769	ambiguous	-0.553	Destabilizing	1.0	D	0.757	deleterious	D	0.539095906	None	None	N
R/Y	0.8044	likely_pathogenic	0.827	pathogenic	-0.322	Destabilizing	1.0	D	0.817	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.