Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002548516 | SCV003269578 | uncertain significance | Multiple congenital anomalies-hypotonia-seizures syndrome 3 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 361 of the PIGT protein (p.Tyr361Cys). This variant is present in population databases (rs781604094, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PIGT-related conditions. ClinVar contains an entry for this variant (Variation ID: 1049999). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002547645 | SCV003569845 | uncertain significance | Inborn genetic diseases | 2022-09-26 | criteria provided, single submitter | clinical testing | The c.1082A>G (p.Y361C) alteration is located in exon 9 (coding exon 9) of the PIGT gene. This alteration results from a A to G substitution at nucleotide position 1082, causing the tyrosine (Y) at amino acid position 361 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001356776 | SCV005388506 | uncertain significance | not provided | 2024-05-01 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Department of Pathology and Laboratory Medicine, |
RCV001356776 | SCV001552036 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The PIGT p.Tyr305Cys variant was not identified in the literature nor was it identified in ClinVar, Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs781604094) and in control databases in 26 of 282618 chromosomes at a frequency of 0.000092 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 10 of 30616 chromosomes (freq: 0.000327), European (non-Finnish) in 15 of 128972 chromosomes (freq: 0.000116) and Latino in 1 of 35428 chromosomes (freq: 0.000028), while the variant was not observed in the African, Ashkenazi Jewish, East Asian, European (Finnish) and Other populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. The p.Tyr305 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |