ClinVar Miner

Submissions for variant NM_016938.5(EFEMP2):c.1217C>T (p.Thr406Met)

gnomAD frequency: 0.00001  dbSNP: rs372299119
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001317566 SCV001508235 uncertain significance Cutis laxa, autosomal recessive, type 1B 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 406 of the EFEMP2 protein (p.Thr406Met). This variant is present in population databases (rs372299119, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with EFEMP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018287). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV004619627 SCV005116492 uncertain significance Cardiovascular phenotype 2024-05-23 criteria provided, single submitter clinical testing The p.T406M variant (also known as c.1217C>T), located in coding exon 10 of the EFEMP2 gene, results from a C to T substitution at nucleotide position 1217. The threonine at codon 406 is replaced by methionine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004770044 SCV005381391 uncertain significance not specified 2024-08-28 criteria provided, single submitter clinical testing Variant summary: EFEMP2 c.1217C>T (p.Thr406Met) results in a non-conservative amino acid change located in the Fibulin, C-terminal Ig-like domain (IPR055088) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251242 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1217C>T in individuals affected with Autosomal Recessive Cutis Laxa and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1018287). Based on the evidence outlined above, the variant was classified as uncertain significance.

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