TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7430	22513;22514;22515	chr2:178722499;178722498;178722497	chr2:179587226;179587225;179587224
N2AB	7113	21562;21563;21564	chr2:178722499;178722498;178722497	chr2:179587226;179587225;179587224
N2A	6186	18781;18782;18783	chr2:178722499;178722498;178722497	chr2:179587226;179587225;179587224
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-59
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1524
• 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
Q/P	rs1324818657	-0.693	0.784	N	0.595	0.322	0.410603549233	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
Q/P	rs1324818657	-0.693	0.784	N	0.595	0.322	0.410603549233	gnomAD-4.0.0	7.96183E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.17237E-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
Q/A	0.3308	likely_benign	0.3071	benign	-0.76	Destabilizing	0.495	N	0.473	neutral	None	None	None	None	N
Q/C	0.8452	likely_pathogenic	0.792	pathogenic	-0.229	Destabilizing	0.995	D	0.592	neutral	None	None	None	None	N
Q/D	0.5897	likely_pathogenic	0.6057	pathogenic	-0.981	Destabilizing	0.329	N	0.429	neutral	None	None	None	None	N
Q/E	0.083	likely_benign	0.0765	benign	-0.834	Destabilizing	0.001	N	0.112	neutral	N	0.38371731	None	None	N
Q/F	0.8799	likely_pathogenic	0.8569	pathogenic	-0.41	Destabilizing	0.944	D	0.645	neutral	None	None	None	None	N
Q/G	0.4153	ambiguous	0.4141	ambiguous	-1.151	Destabilizing	0.704	D	0.513	neutral	None	None	None	None	N
Q/H	0.3768	ambiguous	0.3641	ambiguous	-1.036	Destabilizing	0.006	N	0.306	neutral	N	0.466045118	None	None	N
Q/I	0.5935	likely_pathogenic	0.5376	ambiguous	0.259	Stabilizing	0.944	D	0.639	neutral	None	None	None	None	N
Q/K	0.1858	likely_benign	0.1799	benign	-0.376	Destabilizing	0.27	N	0.385	neutral	N	0.447285999	None	None	N
Q/L	0.2853	likely_benign	0.2625	benign	0.259	Stabilizing	0.642	D	0.523	neutral	N	0.38406124	None	None	N
Q/M	0.5087	ambiguous	0.4742	ambiguous	0.649	Stabilizing	0.981	D	0.549	neutral	None	None	None	None	N
Q/N	0.4488	ambiguous	0.4478	ambiguous	-1.027	Destabilizing	0.704	D	0.43	neutral	None	None	None	None	N
Q/P	0.6721	likely_pathogenic	0.6809	pathogenic	-0.05	Destabilizing	0.784	D	0.595	neutral	N	0.447459357	None	None	N
Q/R	0.2347	likely_benign	0.2285	benign	-0.418	Destabilizing	0.006	N	0.163	neutral	N	0.436068928	None	None	N
Q/S	0.464	ambiguous	0.4627	ambiguous	-1.16	Destabilizing	0.495	N	0.427	neutral	None	None	None	None	N
Q/T	0.3315	likely_benign	0.3036	benign	-0.813	Destabilizing	0.704	D	0.499	neutral	None	None	None	None	N
Q/V	0.3622	ambiguous	0.3187	benign	-0.05	Destabilizing	0.828	D	0.579	neutral	None	None	None	None	N
Q/W	0.8562	likely_pathogenic	0.8351	pathogenic	-0.311	Destabilizing	0.995	D	0.555	neutral	None	None	None	None	N
Q/Y	0.6624	likely_pathogenic	0.631	pathogenic	-0.033	Destabilizing	0.893	D	0.631	neutral	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.