TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19938	60037;60038;60039	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
N2AB	18297	55114;55115;55116	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
N2A	17370	52333;52334;52335	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
N2B	10873	32842;32843;32844	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
Novex-1	10998	33217;33218;33219	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
Novex-2	11065	33418;33419;33420	chr2:178592092;178592091;178592090	chr2:179456819;179456818;179456817
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-32
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1553
• 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/T	rs755204306	-1.166	1.0	N	0.697	0.268	0.46614307118	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.92E-06	0
A/T	rs755204306	-1.166	1.0	N	0.697	0.268	0.46614307118	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
A/T	rs755204306	-1.166	1.0	N	0.697	0.268	0.46614307118	Sasaki (2020)	None	Other	comp het with A9980T, R29293C	None	None	N	Genetic analysis of 2 siblings with asymmetric facial and limb weakness; variant prioritisation; no validation	None	None	None	None	None	None	None	None	None	None	None
A/T	rs755204306	-1.166	1.0	N	0.697	0.268	0.46614307118	gnomAD-4.0.0	3.59616E-05	None	None	None	None	N	None	1.33568E-05	0	None	0	3.58568E-04	None	0	0	2.54347E-05	8.78677E-05	4.80708E-05
A/V	rs1187337182	0.677	0.992	N	0.639	0.354	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.14E-05	0
A/V	rs1187337182	0.677	0.992	N	0.639	0.354	None	gnomAD-3.1.2	4.61E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	8.83E-05	0	0
A/V	rs1187337182	0.677	0.992	N	0.639	0.354	None	gnomAD-4.0.0	7.25416E-05	None	None	None	None	N	None	2.67115E-05	0	None	0	0	None	0	0	9.58025E-05	0	3.20451E-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
A/C	0.4009	ambiguous	0.3985	ambiguous	-0.427	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
A/D	0.9322	likely_pathogenic	0.9599	pathogenic	-2.171	Highly Destabilizing	1.0	D	0.837	deleterious	N	0.496180732	None	None	N
A/E	0.8581	likely_pathogenic	0.9117	pathogenic	-1.901	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
A/F	0.5768	likely_pathogenic	0.6203	pathogenic	-0.49	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
A/G	0.3079	likely_benign	0.3251	benign	-1.244	Destabilizing	0.999	D	0.656	neutral	N	0.493739	None	None	N
A/H	0.8909	likely_pathogenic	0.9242	pathogenic	-1.951	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/I	0.2631	likely_benign	0.2641	benign	0.737	Stabilizing	0.994	D	0.743	deleterious	None	None	None	None	N
A/K	0.9477	likely_pathogenic	0.967	pathogenic	-0.77	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
A/L	0.2375	likely_benign	0.2579	benign	0.737	Stabilizing	0.504	D	0.457	neutral	None	None	None	None	N
A/M	0.4273	ambiguous	0.453	ambiguous	0.539	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
A/N	0.8479	likely_pathogenic	0.8854	pathogenic	-1.264	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
A/P	0.7636	likely_pathogenic	0.7953	pathogenic	0.295	Stabilizing	1.0	D	0.812	deleterious	D	0.523097975	None	None	N
A/Q	0.8138	likely_pathogenic	0.8625	pathogenic	-0.932	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
A/R	0.901	likely_pathogenic	0.9348	pathogenic	-1.154	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
A/S	0.22	likely_benign	0.2324	benign	-1.611	Destabilizing	1.0	D	0.646	neutral	N	0.470354826	None	None	N
A/T	0.1964	likely_benign	0.177	benign	-1.199	Destabilizing	1.0	D	0.697	prob.neutral	N	0.511707545	None	None	N
A/V	0.1306	likely_benign	0.1283	benign	0.295	Stabilizing	0.992	D	0.639	neutral	N	0.383639086	None	None	N
A/W	0.9191	likely_pathogenic	0.9445	pathogenic	-1.416	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/Y	0.7935	likely_pathogenic	0.8413	pathogenic	-0.716	Destabilizing	1.0	D	0.857	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.