Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM5
The NM_176787.5(PIGN):c.1110G>T(p.Gln370His) variant causes a missense change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q370P) has been classified as Likely pathogenic.
PIGN (HGNC:8967): (phosphatidylinositol glycan anchor biosynthesis class N) This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is expressed in the endoplasmic reticulum and transfers phosphoethanolamine (EtNP) to the first mannose of the GPI anchor. Two alternatively spliced variants, which encode an identical isoform, have been reported. [provided by RefSeq, Jul 2008]
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM5
?
PM5 - Novel missense change at an amino acid residue where a different missense change determined to be pathogenic has been seen before
Other missense variant is known to change same aminoacid residue: Variant chr18-62138990-T-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2972897.Status of the report is criteria_provided_single_submitter, 1 stars.
Loss of stability (P = 0.1063);.;Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);.;Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);.;.;Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);.;Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);.;Loss of stability (P = 0.1063);Loss of stability (P = 0.1063);