ClinVar Miner

Submissions for variant NM_000143.3(FH):c.883G>A (p.Ala295Thr) (rs145843819)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166620 SCV000217424 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034485 SCV000043261 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000121091 SCV000085259 not provided not specified 2013-09-19 no assertion provided reference population
Invitae RCV000687788 SCV000815374 uncertain significance Fumarase deficiency 2018-11-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 295 of the FH protein (p.Ala295Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs145843819, ExAC 0.04%). This variant has not been reported in the literature in individuals with FH-related disease. ClinVar contains an entry for this variant (Variation ID: 41583). 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 tolerated, but 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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