ClinVar Miner

Submissions for variant NM_002440.4(MSH4):c.2261C>T (p.Ser754Leu) (rs377712900)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Bioinformatic Lab,Royan Institute RCV001201398 SCV001142647 pathogenic Premature ovarian insufficiency 2019-03-20 criteria provided, single submitter clinical testing Knockout mouse models of MSH4 have been reported to be infertile in both genders due to meiotic arrest (Kneitz, 2000). In human an MSH4 splice site variant has been reported to cause premature ovarian failure (Carlosama, 2017). Exon 17 of this gene encodes a number of functional domains and is highly conserved. Here, we report the S754L variant in exon 17 as the genetic cause of azoospermia and premature ovarian failure in homozygous state and oligozoospermia in the heterozygous state in a consanguineous family.
Clinical Bioinformatic Lab,Royan Institute RCV001255224 SCV001169708 pathogenic Non-obstructive azoospermia 2019-03-20 criteria provided, single submitter clinical testing Knockout mouse models of MSH4 have been reported to be infertile in both genders due to meiotic arrest (Kneitz, 2000). Exon 17 of this gene encodes a number of functional domains and is highly conserved. Here, we report the S754L variant in exon 17 as the genetic cause of non-obstructive azoospermia in homozygous state in a consanguineous family.
Clinical Bioinformatic Lab,Royan Institute RCV001255223 SCV001169709 pathogenic Oligospermia 2019-03-20 criteria provided, single submitter clinical testing Knockout mouse models of MSH4 have been reported to be infertile in both genders due to meiotic arrest (Kneitz, 2000). In human an MSH4 splice site variant has been reported to cause premature ovarian failure (Carlosama, 2017). Exon 17 of this gene encodes a number of functional domains and is highly conserved. Here, we report the S754L variant in exon 17 as the genetic cause of azoospermia and premature ovarian failure in homozygous state and oligozoospermia in the heterozygous state in a consanguineous family.
Institute of Reproductive Genetics, University of Münster RCV001255224 SCV001468894 likely pathogenic Non-obstructive azoospermia 2021-05-24 criteria provided, single submitter research Currently this variant was described in a woman with premature ovarian insufficiency and an additional man with non-obstructive azoospermia, strengthening evidence for the pathogenicity of this variant in context of infertility (Akbari et al, 2021).

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