TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30510	91753;91754;91755	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
N2AB	28869	86830;86831;86832	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
N2A	27942	84049;84050;84051	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
N2B	21445	64558;64559;64560	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
Novex-1	21570	64933;64934;64935	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
Novex-2	21637	65134;65135;65136	chr2:178551003;178551002;178551001	chr2:179415730;179415729;179415728
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-110
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.3249
• 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/E	None	None	0.905	N	0.511	0.218	0.141422826196	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	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
Q/A	0.2051	likely_benign	0.1889	benign	-0.153	Destabilizing	0.984	D	0.575	neutral	None	None	None	None	N
Q/C	0.7891	likely_pathogenic	0.7565	pathogenic	0.179	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
Q/D	0.4499	ambiguous	0.4351	ambiguous	0.006	Stabilizing	0.939	D	0.492	neutral	None	None	None	None	N
Q/E	0.1085	likely_benign	0.1101	benign	-0.051	Destabilizing	0.905	D	0.511	neutral	N	0.33298098	None	None	N
Q/F	0.7349	likely_pathogenic	0.7016	pathogenic	-0.541	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
Q/G	0.3438	ambiguous	0.3403	ambiguous	-0.271	Destabilizing	0.968	D	0.669	prob.neutral	None	None	None	None	N
Q/H	0.298	likely_benign	0.2714	benign	-0.236	Destabilizing	0.994	D	0.583	neutral	N	0.447231992	None	None	N
Q/I	0.3994	ambiguous	0.3696	ambiguous	0.059	Stabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
Q/K	0.1459	likely_benign	0.1412	benign	0.178	Stabilizing	0.958	D	0.537	neutral	N	0.417639804	None	None	N
Q/L	0.164	likely_benign	0.1511	benign	0.059	Stabilizing	0.979	D	0.66	prob.neutral	N	0.426318002	None	None	N
Q/M	0.3979	ambiguous	0.3753	ambiguous	0.328	Stabilizing	0.998	D	0.624	neutral	None	None	None	None	N
Q/N	0.2852	likely_benign	0.2541	benign	-0.076	Destabilizing	0.147	N	0.254	neutral	None	None	None	None	N
Q/P	0.1315	likely_benign	0.1212	benign	0.013	Stabilizing	0.998	D	0.616	neutral	N	0.396205739	None	None	N
Q/R	0.1668	likely_benign	0.1687	benign	0.301	Stabilizing	0.979	D	0.501	neutral	N	0.430819745	None	None	N
Q/S	0.257	likely_benign	0.2323	benign	-0.071	Destabilizing	0.968	D	0.507	neutral	None	None	None	None	N
Q/T	0.2434	likely_benign	0.2249	benign	0.005	Stabilizing	0.968	D	0.525	neutral	None	None	None	None	N
Q/V	0.2455	likely_benign	0.2273	benign	0.013	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
Q/W	0.7566	likely_pathogenic	0.7457	pathogenic	-0.569	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
Q/Y	0.5476	ambiguous	0.514	ambiguous	-0.283	Destabilizing	0.998	D	0.627	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.