Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000177253 | SCV000229096 | likely benign | not specified | 2017-03-27 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000274096 | SCV000456754 | uncertain significance | Pituitary hormone deficiency, combined, 2 | 2018-01-12 | 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 |
RCV000896336 | SCV001040422 | benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000896336 | SCV003798904 | uncertain significance | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | Identified as heterozygous in two unrelated patients in published literature presenting with either amenorrhea or pituitary stalk interruption syndrome (Delaney et al., 2020; Hietamki et al., 2022); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 36034425, 32870266, 35875813) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000177253 | SCV005075826 | uncertain significance | not specified | 2024-04-02 | criteria provided, single submitter | clinical testing | Variant summary: PROP1 c.425C>T (p.Ala142Val) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.002 in 251096 control chromosomes (gnomAD). c.425C>T has been reported in the literature in individuals affected with Hypothalamic amenorrhoea or pituitary stalk interruption syndrome without strong evidence of causality (e.g. Delaney_2021, Dwyer_2022, Brauner_2023). These reports do not provide unequivocal conclusions about association of the variant with Combined Pituitary Hormone Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32870266, 36407308, 38096238). ClinVar contains an entry for this variant (Variation ID: 196432). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV000274096 | SCV001457801 | likely benign | Pituitary hormone deficiency, combined, 2 | 2020-01-05 | no assertion criteria provided | clinical testing | |
Laboratory of Diagnostic Genome Analysis, |
RCV000896336 | SCV001799124 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000896336 | SCV001925179 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000896336 | SCV001964310 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Yale Center for Mendelian Genomics, |
RCV001849329 | SCV002106773 | uncertain significance | Amenorrhea | 2021-03-08 | no assertion criteria provided | literature only |