ClinVar Miner

Submissions for variant NM_000361.3(THBD):c.415G>T (p.Ala139Ser)

gnomAD frequency: 0.00002  dbSNP: rs982068192
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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 RCV002030316 SCV002268053 uncertain significance not provided 2025-01-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 139 of the THBD protein (p.Ala139Ser). 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 THBD-related conditions. ClinVar contains an entry for this variant (Variation ID: 1485061). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt THBD protein function with a negative predictive value of 80%. 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 RCV002479668 SCV002789323 uncertain significance Atypical hemolytic-uremic syndrome with thrombomodulin anomaly; Thrombomodulin-related bleeding disorder 2024-02-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV004671593 SCV005170892 uncertain significance Inborn genetic diseases 2024-03-19 criteria provided, single submitter clinical testing The c.415G>T (p.A139S) alteration is located in exon 1 (coding exon 1) of the THBD gene. This alteration results from a G to T substitution at nucleotide position 415, causing the alanine (A) at amino acid position 139 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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