ClinVar Miner

Submissions for variant NM_004278.4(PIGL):c.438C>A (p.Phe146Leu)

dbSNP: rs773591135
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003222348 SCV003918483 likely pathogenic not provided 2023-04-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 35378319)
Corniche Hospital, Abu Dhabi, Abu Dhabi Health Services Co - SEHA RCV002274225 SCV002097245 likely pathogenic Hyperphosphatasia with intellectual disability syndrome 1; CHIME syndrome 2021-09-29 no assertion criteria provided clinical testing Three siblings with homozygous c.438C>A, p.(Phe146Leu) variants in PIGL were affected with multiple congenital anomalies which presented prenatally. Anomalies included cleft palate, left-sided congenital diaphragmatic hernia (CDH), vermian hypoplasia, dilated renal pelvis, and 2/3 had polyhydramnios, ambiguous genitalia/micropenis and dysmorphic facial features. All three died within hours of preterm birth, likely due to CDH. The couple conceived using IVF and PGT-M to select for no PIGL c.438C>A variants, resulting in the couple's fouth baby, born a health male.
GenomeConnect, ClinGen RCV002508967 SCV002818441 not provided PIGL-related disorder no assertion provided phenotyping only Variant classified as Likely pathogenic and reported on 06-14-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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