ClinVar Miner

Submissions for variant NM_000388.4(CASR):c.2915C>T (p.Thr972Met) (rs200620134)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000664401 SCV000440131 uncertain significance Hypocalciuric hypercalcemia, familial, type 1 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 Clinical Services Laboratory,Illumina RCV000288087 SCV000440132 uncertain significance Hypocalcemia, autosomal dominant 1 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 Clinical Services Laboratory,Illumina RCV000345436 SCV000440133 uncertain significance Neonatal severe hyperparathyroidism 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 Clinical Services Laboratory,Illumina RCV000383567 SCV000440134 benign Familial isolated hypoparathyroidism 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000525899 SCV000638059 uncertain significance Familial hypocalciuric hypercalcemia; Hypocalcemia, autosomal dominant 1 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 972 of the CASR protein (p.Thr972Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs200620134, ExAC 0.02%). This variant has been reported in an individual with an atypical presentation of  familial benign hypocalciuric hypercalcemia (FHH) and in his unaffected son (PMID: 25292184).  This variant has also been reported in an individual affected with hyperparathyroidism (PMID: 26646938). ClinVar contains an entry for this variant (Variation ID: 342802). Experimental studies have suggested that this missense change may negatively impact CASR protein function (PMID: 25292184). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Athena Diagnostics Inc RCV000711038 SCV000841358 uncertain significance not provided 2018-01-29 criteria provided, single submitter clinical testing
Mendelics RCV000664401 SCV001136578 uncertain significance Hypocalciuric hypercalcemia, familial, type 1 2019-05-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV001016922 SCV001177929 uncertain significance Inborn genetic diseases 2019-05-21 criteria provided, single submitter clinical testing Insufficient evidence
OMIM RCV000664401 SCV000788331 pathogenic Hypocalciuric hypercalcemia, familial, type 1 2018-07-25 no assertion criteria provided literature only

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