ClinVar Miner

Submissions for variant NM_000479.5(AMH):c.295A>T (p.Thr99Ser)

gnomAD frequency: 0.00029  dbSNP: rs200226465
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001786785 SCV002028723 uncertain significance not provided 2021-11-23 criteria provided, single submitter clinical testing Identified in the heterozygous state in a male with congenital hypogonadotropic hypogonadism and in two females with polycystic ovarian syndrome (Gorsic et al., 2019; Malone et al., 2019); Published functional studies suggest a damaging effect on AMH activity, AMH protein secretion, and downstream signaling (Gorsic et al., 2019; Malone et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28505284, 31291191, 30786001)
Labcorp Genetics (formerly Invitae), Labcorp RCV001786785 SCV002151336 uncertain significance not provided 2024-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 99 of the AMH protein (p.Thr99Ser). This variant is present in population databases (rs200226465, gnomAD 0.04%). This missense change has been observed in individual(s) with hypogonadotropic hypogonadism (PMID: 31291191). ClinVar contains an entry for this variant (Variation ID: 1326605). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects AMH function (PMID: 30786001, 31291191). 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.
Fulgent Genetics, Fulgent Genetics RCV002478018 SCV002788473 uncertain significance Persistent Mullerian duct syndrome 2021-12-20 criteria provided, single submitter clinical testing

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