ClinVar Miner

Submissions for variant NM_001042545.2(LTBP4):c.4037dup (p.Arg1347fs)

dbSNP: rs606231161
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002510768 SCV002820614 likely pathogenic not provided 2022-07-11 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation; however, other loss-of-function variants have not been reported downstream in HGMD and functional data suggests that this variant may not result in complete nonsense mediated decay (PMID: 22829427); Reported as c.4128insC; observed in unknown phase with c.2570_2571delGCinsAA in a patient with cutis laxa (PMID: 19836010). Of note, the mother was reported to be negative for both variants and the father was not tested.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22829427, 19836010)
Labcorp Genetics (formerly Invitae), Labcorp RCV002510768 SCV003443912 pathogenic not provided 2023-08-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1377Alafs*27) in the LTBP4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LTBP4 are known to be pathogenic (PMID: 19836010, 22829427). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with cutis laxa (PMID: 19836010, 25882708). This variant is also known as c.4128insC (p.P1376fsX1403). ClinVar contains an entry for this variant (Variation ID: 5399). Studies have shown that this premature translational stop signal does not significantly alter or has an unclear effect on LTBP4 gene expression (PMID: 22829427). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000005730 SCV000025912 pathogenic Cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies 2013-01-01 no assertion criteria provided literature only

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