Submissions for variant NM_000527.5(LDLR):c.911A>T (p.Asp304Val)

dbSNP: rs1555803898

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000508698	SCV002505657	uncertain significance	Hypercholesterolemia, familial, 1	2022-03-18	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.911A>T (p.Asp304Val) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PM5 and PP3 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met. PM5 - 4 other missense variants in the same codon: - NNM_000527.5(LDLR):c.910G>A (p.Asp304Asn) (ClinVar ID 3692) - Pathogenic by these guidelines - NM_000527.5(LDLR):c.910G>C (p.Asp304His) (ClinVar ID 440612) - VUS by these guidelines - NM_000527.5(LDLR):c.912C>G (p.Asp304Glu) (ClinVar ID 226336) - Likely pathogenic by these guidelines - NM_000527.5(LDLR):c.910G>T (p.Asp304Tyr) (ClinVar ID 251517) - Likely pathogenic by these guidelines There is 1 variant in the same codon classified as Pathogenic by these guidelines, so PM5 is Met. PP3 - REVEL = 0.985. It is above 0.75, so PP3 is Met.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000508698	SCV000606266	pathogenic	Hypercholesterolemia, familial, 1		no assertion criteria provided	research