ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.315T>G (p.Ile105Met)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002320929 SCV002610098 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-31 criteria provided, single submitter clinical testing The p.I105M variant (also known as c.315T>G), located in coding exon 4 of the RAD51D gene, results from a T to G substitution at nucleotide position 315. The isoleucine at codon 105 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003528369 SCV004297753 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 105 of the RAD51D protein (p.Ile105Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 28767289). This variant is also known as c.375A>C. ClinVar contains an entry for this variant (Variation ID: 1728297). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RAD51D protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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