NM_000388.4(CASR):c.367T>A (p.Leu123Met) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 7, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002016645.4

Allele description [Variation Report for NM_000388.4(CASR):c.367T>A (p.Leu123Met)]

NM_000388.4(CASR):c.367T>A (p.Leu123Met)

Gene:

CASR:calcium sensing receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q21.1

Genomic location:

Preferred name:

NM_000388.4(CASR):c.367T>A (p.Leu123Met)

HGVS:

NC_000003.12:g.122257262T>A
NG_009058.2:g.78595T>A
NM_000388.4:c.367T>AMANE SELECT
NM_001178065.2:c.367T>A
NP_000379.3:p.Leu123Met
NP_001171536.2:p.Leu123Met
NC_000003.11:g.121976109T>A
NG_009058.1:g.78580T>A

Protein change:

L123M

Links:

dbSNP: rs2107627702

NCBI 1000 Genomes Browser:

rs2107627702

Molecular consequence:

NM_000388.4:c.367T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178065.2:c.367T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hypocalciuric hypercalcemia (FHH)
Synonyms:: Familial benign hypercalcemia
Identifiers:: MONDO: MONDO:0018458; MedGen: C1809471; OMIM: PS145980

Name:: Autosomal dominant hypocalcemia 1 (HYPOC1)
Synonyms:: HYPOCALCEMIA, FAMILIAL
Identifiers:: MONDO: MONDO:0011013; MedGen: C0342345; OMIM: 601198

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002302040	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30407919, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002302040

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 7, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Novel mutations associated with inherited human calcium-sensing receptor disorders: A clinical genetic study.

García-Castaño A, Madariaga L, Pérez de Nanclares G, Ariceta G, Gaztambide S, Castaño L.

Eur J Endocrinol. 2019 Jan 1;180(1):59-70. doi: 10.1530/EJE-18-0129.

PubMed [citation]

PMID:: 30407919

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002302040.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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"). 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. ClinVar contains an entry for this variant (Variation ID: 1511340). This missense change has been observed in individual(s) with CASR-related conditions (PMID: 30407919). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 123 of the CASR protein (p.Leu123Met).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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