Submissions for variant NM_001927.4(DES):c.-6G>A

gnomAD frequency: 0.00003  dbSNP: rs774967446

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000289026	SCV000427666	uncertain significance	Neurogenic scapuloperoneal syndrome, Kaeser type	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.
Illumina Laboratory Services, Illumina	RCV000327635	SCV000427667	uncertain significance	Myofibrillar Myopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV002265737	SCV000427668	uncertain significance	Desmin-related myofibrillar myopathy	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.
Illumina Laboratory Services, Illumina	RCV000283203	SCV000427669	uncertain significance	Dilated cardiomyopathy 1I	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001293589	SCV001482204	uncertain significance	not specified	2021-02-01	criteria provided, single submitter	clinical testing	Variant summary: DES c.-6G>A is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 2.9e-05 in 206062 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.-6G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.