ClinVar Miner

Submissions for variant NM_000156.6(GAMT):c.511C>G (p.Leu171Val)

gnomAD frequency: 0.00005  dbSNP: rs770110177
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187568 SCV000241162 uncertain significance not provided 2013-02-22 criteria provided, single submitter clinical testing p.Leu171Val (CTC>GTC): c.511 C>G in exon 5 of the GAMT gene (NM_000156.4) The Leu171Val missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Leu171Val in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. It alters a well-conserved position in the GAMT gene, and missense mutations have been reported at nearby codons in association with GAMT deficiency. However, amino acid substitution is conservative, as both Leucine and Valine are uncharged, non-polar amino acids. Additionally, multiple in silico algorithms predict Leu171Val may be benign. Therefore, based on the currently available information, it is unclear whether Leu171Val is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Fulgent Genetics, Fulgent Genetics RCV001827999 SCV002776710 uncertain significance Deficiency of guanidinoacetate methyltransferase 2021-07-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002516991 SCV003454916 uncertain significance Cerebral creatine deficiency syndrome 2022-02-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 171 of the GAMT protein (p.Leu171Val). This variant is present in population databases (rs770110177, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GAMT-related conditions. ClinVar contains an entry for this variant (Variation ID: 205583). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Natera, Inc. RCV001827999 SCV002087020 uncertain significance Deficiency of guanidinoacetate methyltransferase 2019-10-28 no assertion criteria provided clinical testing

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