ClinVar Miner

Submissions for variant NM_015295.3(SMCHD1):c.2731T>A (p.Leu911Ile)

gnomAD frequency: 0.00002  dbSNP: rs770371694
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543644 SCV000638437 uncertain significance Facioscapulohumeral muscular dystrophy 2 2023-06-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 464165). This variant has not been reported in the literature in individuals affected with SMCHD1-related conditions. This variant is present in population databases (rs770371694, gnomAD 0.07%). This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 911 of the SMCHD1 protein (p.Leu911Ile). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SMCHD1 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 RCV004669036 SCV005171272 uncertain significance Inborn genetic diseases 2024-03-16 criteria provided, single submitter clinical testing The c.2731T>A (p.L911I) alteration is located in exon 22 (coding exon 22) of the SMCHD1 gene. This alteration results from a T to A substitution at nucleotide position 2731, causing the leucine (L) at amino acid position 911 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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