ClinVar Miner

Submissions for variant NM_006493.4(CLN5):c.1048A>G (p.Ile350Val)

gnomAD frequency: 0.00006  dbSNP: rs762333226
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820427 SCV000961139 uncertain significance Neuronal ceroid lipofuscinosis 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 399 of the CLN5 protein (p.Ile399Val). This variant is present in population databases (rs762333226, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 662712). 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 CLN5 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.
GeneDx RCV001546138 SCV001765605 uncertain significance not provided 2023-08-02 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously reported as pathogenic or benign to our knowledge
Genome-Nilou Lab RCV001275306 SCV002027080 uncertain significance Neuronal ceroid lipofuscinosis 5 2021-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV002537470 SCV003694382 uncertain significance Inborn genetic diseases 2022-08-03 criteria provided, single submitter clinical testing The c.1195A>G (p.I399V) alteration is located in exon 4 (coding exon 4) of the CLN5 gene. This alteration results from a A to G substitution at nucleotide position 1195, causing the isoleucine (I) at amino acid position 399 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275306 SCV001460328 uncertain significance Neuronal ceroid lipofuscinosis 5 2020-04-16 no assertion criteria provided clinical testing

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