NM_000316.3(PTH1R):c.401A>C (p.Tyr134Ser) AND Eiken syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 11, 2019
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:: RCV000855713.6

Allele description [Variation Report for NM_000316.3(PTH1R):c.401A>C (p.Tyr134Ser)]

NM_000316.3(PTH1R):c.401A>C (p.Tyr134Ser)

Gene:

PTH1R:parathyroid hormone 1 receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000316.3(PTH1R):c.401A>C (p.Tyr134Ser)

Other names:

PTHR

HGVS:

NC_000003.12:g.46897942A>C
NG_008864.1:g.25197A>C
NM_000316.3:c.401A>CMANE SELECT
NM_001184744.1:c.401A>C
NP_000307.1:p.Tyr134Ser
NP_001171673.1:p.Tyr134Ser
NC_000003.11:g.46939432A>C

Protein change:

Y134S; TYR134SER

Links:

OMIM: 168468.0016; dbSNP: rs1575520937

NCBI 1000 Genomes Browser:

rs1575520937

Molecular consequence:

NM_000316.3:c.401A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001184744.1:c.401A>C - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Uncertain function

Observations:

Condition(s)

Name:: Eiken syndrome (EKNS)
Synonyms:: BONE MODELING DEFECT OF HANDS AND FEET; Eiken skeletal dysplasia
Identifiers:: MONDO: MONDO:0010803; MedGen: C1838779; Orphanet: 79106; OMIM: 600002

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000902435	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001745210	OMIM	no assertion criteria provided	Pathogenic (Jul 6, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000902435

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001745210

OMIM

no assertion criteria provided

Pathogenic
(Jul 6, 2021)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
Asian	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Report of second case and clinical and molecular characterization of Eiken syndrome.

Moirangthem A, Narayanan DL, Jacob P, Nishimura G, Mortier G, Girisha KM.

Clin Genet. 2018 Nov;94(5):457-460. doi: 10.1111/cge.13413. Epub 2018 Jul 27.

PubMed [citation]

PMID:: 29987841

The third family with Eiken syndrome.

Jacob P, Soni JP, Mortier G, Girisha KM.

Clin Genet. 2019 Oct;96(4):378-379. doi: 10.1111/cge.13601. Epub 2019 Jul 11. No abstract available.

PubMed [citation]

PMID:: 31297790

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV000902435.1

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

Description

A novel variant, c.401A>C is identified in PTH1R gene, which is known to cause Eiken syndrome. The variant is observed in heterozygous state in both the parents and is found in wild type or heterozygous state in the siblings. The phenotype of the patient is in concordance with the condition. Hence, according to ACMG guidelines the variant is interpreted to be of uncertain significance. Functional characterization of the variant is recommended before clinical utility.

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

From OMIM, SCV001745210.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 6-year-old Indian boy with Eiken syndrome (EKNS; 600002), Jacob et al. (2019) identified homozygosity for a c.401A-C transversion (c.401A-C, NM_000316.3) in the PTH1R gene, resulting in a tyr134-to-ser (Y134S) substitution. The mutation segregated with disease in the family and was not found in an in-house exome database or in public variant databases.

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

Last Updated: Feb 25, 2023

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