ClinVar Miner

Submissions for variant NM_001918.4(DBT):c.939G>C (p.Lys313Asn) (rs398123676)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000790732 SCV000232154 pathogenic not provided 2013-09-04 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000179839 SCV000240048 pathogenic Maple syrup urine disease 2013-01-01 criteria provided, single submitter research
Counsyl RCV000179839 SCV000791370 likely pathogenic Maple syrup urine disease 2017-05-16 criteria provided, single submitter clinical testing
Invitae RCV000179839 SCV001410080 pathogenic Maple syrup urine disease 2020-02-18 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 313 of the DBT protein (p.Lys313Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant also falls at the last nucleotide of exon 7 of the DBT coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs398123676, ExAC 0.02%). This variant has been observed in several individuals affected with maple syrup urine disease (PMID: 26257134, 18378174). ClinVar contains an entry for this variant (Variation ID: 94017). 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: Probably Damaging; Align-GVGD: Class C0). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Centogene AG - the Rare Disease Company RCV001250158 SCV001424399 pathogenic Maple syrup urine disease type 2 criteria provided, single submitter clinical testing

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