NM_003235.5(TG):c.229G>A (p.Gly77Ser) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 18, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000501874.10

Allele description [Variation Report for NM_003235.5(TG):c.229G>A (p.Gly77Ser)]

NM_003235.5(TG):c.229G>A (p.Gly77Ser)

Gene:

TG:thyroglobulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.22

Genomic location:

Preferred name:

NM_003235.5(TG):c.229G>A (p.Gly77Ser)

HGVS:

NC_000008.11:g.132869781G>A
NG_015832.1:g.7822G>A
NM_003235.5:c.229G>AMANE SELECT
NP_003226.4:p.Gly77Ser
NC_000008.10:g.133882026G>A
NM_003235.4:c.229G>A
p.Gly77Ser

Protein change:

G77S

Links:

dbSNP: rs142698837

NCBI 1000 Genomes Browser:

rs142698837

Molecular consequence:

NM_003235.5:c.229G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000597479	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 7, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000966240	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jul 18, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29590070, 10403171, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000597479

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 7, 2016)

germline

clinical testing

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

SCV000966240

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jul 18, 2018)

germline

clinical testing

PubMed (3)
[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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

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; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.

Bastarache L, Hughey JJ, Hebbring S, Marlo J, Zhao W, Ho WT, Van Driest SL, McGregor TL, Mosley JD, Wells QS, Temple M, Ramirez AH, Carroll R, Osterman T, Edwards T, Ruderfer D, Velez Edwards DR, Hamid R, Cogan J, Glazer A, Wei WQ, Feng Q, et al.

Science. 2018 Mar 16;359(6381):1233-1239. doi: 10.1126/science.aal4043.

PubMed [citation]

PMID:: 29590070
PMCID:: PMC5959723

See all PubMed Citations (4)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000597479.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000966240.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly77Ser variant in TG has been reported in the homozygous state in 3 individuals with co ngenital hypothyroidism (van de Graaf 1999) and has been reported in ClinVar (Va riation ID: 436996). This variant has been identified in 0.13% (167/126550) of E uropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.br oadinstitute.org; dbSNP rs142698837). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic r ole. In vitro functional studies suggest that the p.Gly77Ser variant leads to th e use of an alternative splice site (Bastarache 2018); however, these types of a ssays may not accurately represent biological function. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this varia nt is uncertain. ACMG/AMP criteria applied: PS4_Moderate, PS3_Supporting, PM3_Su pporting.

#	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		1	not provided	1	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine