ClinVar Miner

Submissions for variant NM_001386140.1(MTTP):c.1783C>T (p.Arg595Ter)

gnomAD frequency: 0.00001  dbSNP: rs199422219
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000015303 SCV001360911 pathogenic Abetalipoproteinaemia 2022-02-07 criteria provided, single submitter clinical testing Variant summary: MTTP c.1783C>T (p.Arg595X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.2593G>T (p.Gly865X)). The variant was absent in 251426 control chromosomes (gnomAD) but has been reported in the literature in individuals affected with Abetalipoproteinaemia (e.g. Bassen-Kornzweig Syndrome; Chardon_2009, Ohashi_2000, Sharp_1993). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001851870 SCV002240203 pathogenic not provided 2022-07-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 14235). This premature translational stop signal has been observed in individual(s) with clinical features of abetalipoproteinemia (PMID: 8361539). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg595*) in the MTTP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MTTP are known to be pathogenic (PMID: 8533758, 9671739).
PreventionGenetics, part of Exact Sciences RCV003398517 SCV004109944 pathogenic MTTP-related disorder 2023-03-14 criteria provided, single submitter clinical testing The MTTP c.1783C>T variant is predicted to result in premature protein termination (p.Arg595*). This variant was reported in the homozygous state in an individual with abetalipoproteinaemia (Sharp et al. 1993. PubMed ID: 8361539). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in MTTP are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000015303 SCV000035562 pathogenic Abetalipoproteinaemia 1993-09-02 no assertion criteria provided literature only
Natera, Inc. RCV000015303 SCV002082445 pathogenic Abetalipoproteinaemia 2021-01-25 no assertion criteria provided clinical testing

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