ClinVar Miner

Submissions for variant NM_004429.5(EFNB1):c.365T>C (p.Met122Thr)

dbSNP: rs1556106318
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519575 SCV000616707 likely pathogenic not provided 2017-08-17 criteria provided, single submitter clinical testing The M122T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant has been observed as apparently de novo in a patient at GeneDx. It is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). M122T is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within the dimerization domain that is conserved in mammals; this domain is conserved between the three ephrin-B proteins (Himanen et al., 2001). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp RCV000519575 SCV003202181 uncertain significance not provided 2022-05-22 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 449016). This variant has not been reported in the literature in individuals affected with EFNB1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 122 of the EFNB1 protein (p.Met122Thr).

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