ClinVar Miner

Submissions for variant NM_005334.3(HCFC1):c.4574C>T (p.Thr1525Ile)

gnomAD frequency: 0.00004  dbSNP: rs782370174
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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 RCV001992205 SCV002284089 uncertain significance Methylmalonic acidemia with homocystinuria, type cblX 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 1525 of the HCFC1 protein (p.Thr1525Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs782370174, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with HCFC1-related conditions. 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: "Benign"; 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.
Fulgent Genetics, Fulgent Genetics RCV001992205 SCV002784384 uncertain significance Methylmalonic acidemia with homocystinuria, type cblX 2022-05-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003250399 SCV003951656 uncertain significance Inborn genetic diseases 2023-04-28 criteria provided, single submitter clinical testing The c.4574C>T (p.T1525I) alteration is located in exon 19 (coding exon 19) of the HCFC1 gene. This alteration results from a C to T substitution at nucleotide position 4574, causing the threonine (T) at amino acid position 1525 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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