ClinVar Miner

Submissions for variant NM_006514.4(SCN10A):c.4514C>T (p.Thr1505Met)

gnomAD frequency: 0.00006  dbSNP: rs184521520
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000697894 SCV000826527 uncertain significance Brugada syndrome 2024-08-10 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1505 of the SCN10A protein (p.Thr1505Met). This variant is present in population databases (rs184521520, gnomAD 0.04%). This missense change has been observed in individual(s) with neuromuscular disease (PMID: 28078312). ClinVar contains an entry for this variant (Variation ID: 575624). 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 SCN10A 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.
GeneDx RCV001568539 SCV001792426 uncertain significance not provided 2021-06-03 criteria provided, single submitter clinical testing Identified in homozygous state in a Sudanese family with progressive neuromuscular disease, severe cognitive impairment, muscle weakness, upper motor neuron lesion, anhydrosis, facial dysmorphism, and recurrent seizures but with no cardiac findings (Kambouris et al., 2017); Reported as a variant of uncertain significance in ClinVar (ClinVar Variation ID#575624; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 28078312)
Ambry Genetics RCV002334335 SCV002639747 likely benign Cardiovascular phenotype 2020-09-14 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002493213 SCV002777578 uncertain significance Episodic pain syndrome, familial, 2 2021-09-04 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV001568539 SCV001920983 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001568539 SCV001964261 uncertain significance not provided no assertion criteria provided clinical testing

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