Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001944867 | SCV002135562 | pathogenic | Lethal multiple pterygium syndrome | 2023-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 312 of the CHRNA1 protein (p.Thr312Asn). This variant is present in population databases (rs746404398, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of autosomal dominant congenital myasthenic syndrome (Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1366831). 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 CHRNA1 protein function. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002478159 | SCV002778058 | uncertain significance | Lethal multiple pterygium syndrome; Myasthenic syndrome, congenital, 1B, fast-channel; Congenital myasthenic syndrome 1A | 2022-01-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003303242 | SCV004002347 | uncertain significance | Inborn genetic diseases | 2023-03-31 | criteria provided, single submitter | clinical testing | The c.935C>A (p.T312N) alteration is located in exon 7 (coding exon 7) of the CHRNA1 gene. This alteration results from a C to A substitution at nucleotide position 935, causing the threonine (T) at amino acid position 312 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |