NM_000369.5(TSHR):c.1891T>G (p.Phe631Val) AND Familial hyperthyroidism due to mutations in TSH receptor

Germline classification:: Likely pathogenic (1 submission)
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:: RCV003314474.1

Allele description [Variation Report for NM_000369.5(TSHR):c.1891T>G (p.Phe631Val)]

NM_000369.5(TSHR):c.1891T>G (p.Phe631Val)

Gene:

TSHR:thyroid stimulating hormone receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q31.1

Genomic location:

Preferred name:

NM_000369.5(TSHR):c.1891T>G (p.Phe631Val)

HGVS:

NC_000014.9:g.81143949T>G
NG_009206.1:g.193425T>G
NM_000369.5:c.1891T>GMANE SELECT
NP_000360.2:p.Phe631Val
NP_000360.2:p.Phe631Val
LRG_523t1:c.1891T>G
LRG_523:g.193425T>G
LRG_523p1:p.Phe631Val
NC_000014.8:g.81610293T>G
NM_000369.2:c.1891T>G

Protein change:

F631V

Molecular consequence:

NM_000369.5:c.1891T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial hyperthyroidism due to mutations in TSH receptor
Synonyms:: HYPERTHYROIDISM, CONGENITAL NONAUTOIMMUNE; HYPERTHYROIDISM, NONAUTOIMMUNE, AUTOSOMAL DOMINANT; TOXIC THYROID HYPERPLASIA, AUTOSOMAL DOMINANT; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0012203; MedGen: C1836706; Orphanet: 424; OMIM: 609152

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004013860	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7800007, 16756474, 15876166, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004013860

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

unknown

clinical testing

PubMed (4)
[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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nothing to display

See all PubMed Citations (4)

Details of each submission

From 3billion, SCV004013860.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Functional studies provide moderate evidence of having a damaging effect on the gene or gene product (PMID: 15876166). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.85; 3Cnet: 0.78). The same nucleotide change resulting in the same amino acid change has been previously reported to be associated with TSHR-related disorder (PMID: 15876166). Different missense changes at the the same codon (p.Phe631Leu, p.Phe631Ser) have been reported to be associated with TSHR-related disorder (ClinVar ID: VCV000006433/PMID: 16756474, 7800007). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Jul 22, 2023

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