ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.465T>G (p.Asn155Lys)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002330488 SCV002633780 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-14 criteria provided, single submitter clinical testing The p.N155K variant (also known as c.465T>G), located in coding exon 5 of the SDHA gene, results from a T to G substitution at nucleotide position 465. The asparagine at codon 155 is replaced by lysine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003775944 SCV004577674 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 155 of the SDHA protein (p.Asn155Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1742252). 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 SDHA protein function with a negative predictive value of 95%. 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.

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