ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3616G>T (p.Ala1206Ser) (rs1555587407)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000510023 SCV000608094 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-31 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Integrated Genetics/Laboratory Corporation of America RCV000590578 SCV000699046 uncertain significance not provided 2016-05-02 criteria provided, single submitter clinical testing Variant summary: The c.3616G>T variant affects a non-conserved nucleotide, resulting in amino acid change from Ala to Ser. 4/4 in-silico tools predict benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is not found in 120884 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One reputable clinical lab has classified the variant as a VUS. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000701491 SCV000830294 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-04-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 1206 of the BRCA1 protein (p.Ala1206Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 441433). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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