ClinVar Miner

Submissions for variant NM_003480.4(MFAP5):c.395A>T (p.His132Leu)

gnomAD frequency: 0.00002  dbSNP: rs374890052
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497983 SCV000590145 uncertain significance not provided 2020-08-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); 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; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015)
Labcorp Genetics (formerly Invitae), Labcorp RCV000497983 SCV002188164 uncertain significance not provided 2021-06-15 criteria provided, single submitter clinical testing 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with MFAP5-related conditions. ClinVar contains an entry for this variant (Variation ID: 432423). This variant is present in population databases (rs374890052, ExAC 0.004%). This sequence change replaces histidine with leucine at codon 132 of the MFAP5 protein (p.His132Leu). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and leucine.
Ambry Genetics RCV002376910 SCV002624030 uncertain significance Cardiovascular phenotype 2022-07-17 criteria provided, single submitter clinical testing The p.H132L variant (also known as c.395A>T), located in coding exon 8 of the MFAP5 gene, results from an A to T substitution at nucleotide position 395. The histidine at codon 132 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003750797 SCV004563791 uncertain significance Aortic aneurysm, familial thoracic 9 2023-09-19 criteria provided, single submitter clinical testing The MFAP5 c.395A>T; p.His132Leu variant (rs374890052), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 432423). This variant is found in the general population with an overall allele frequency of 0.0021% (6/282794 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.347). Due to limited information, the clinical significance of this variant is uncertain at this time.

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