ClinVar Miner

Submissions for variant NM_000360.4(TH):c.649G>A (p.Asp217Asn)

gnomAD frequency: 0.00003  dbSNP: rs371488205
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001988353 SCV002269142 uncertain significance Autosomal recessive DOPA responsive dystonia 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 248 of the TH protein (p.Asp248Asn). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with TH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1481526). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002579556 SCV003607488 uncertain significance Inborn genetic diseases 2022-03-11 criteria provided, single submitter clinical testing The c.742G>A (p.D248N) alteration is located in exon 7 (coding exon 7) of the TH gene. This alteration results from a G to A substitution at nucleotide position 742, causing the aspartic acid (D) at amino acid position 248 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004784025 SCV005396684 uncertain significance not provided 2024-05-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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