ClinVar Miner

Submissions for variant NM_031935.3(HMCN1):c.13966A>G (p.Ser4656Gly)

gnomAD frequency: 0.00007  dbSNP: rs776783939
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001096682 SCV001252907 uncertain significance Age related macular degeneration 1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV002557983 SCV003272492 uncertain significance not provided 2022-10-19 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 874051). This missense change has been observed in individuals with clinical features of autosomal dominant inherited retinal dystrophy (Invitae). This variant is present in population databases (rs776783939, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 4656 of the HMCN1 protein (p.Ser4656Gly).
Genome-Nilou Lab RCV001096682 SCV004180597 uncertain significance Age related macular degeneration 1 2023-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004032012 SCV004883084 uncertain significance not specified 2022-11-03 criteria provided, single submitter clinical testing The c.13966A>G (p.S4656G) alteration is located in exon 90 (coding exon 90) of the HMCN1 gene. This alteration results from a A to G substitution at nucleotide position 13966, causing the serine (S) at amino acid position 4656 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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