NM_000545.8(HNF1A):c.502C>T (p.Arg168Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 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:: RCV003002133.2

Allele description [Variation Report for NM_000545.8(HNF1A):c.502C>T (p.Arg168Cys)]

NM_000545.8(HNF1A):c.502C>T (p.Arg168Cys)

Gene:

HNF1A:HNF1 homeobox A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.31

Genomic location:

Preferred name:

NM_000545.8(HNF1A):c.502C>T (p.Arg168Cys)

HGVS:

NC_000012.12:g.120989008C>T
NG_011731.2:g.15263C>T
NM_000545.8:c.502C>TMANE SELECT
NM_001306179.2:c.502C>T
NM_001406915.1:c.502C>T
NP_000536.5:p.Arg168Cys
NP_000536.6:p.Arg168Cys
NP_001293108.2:p.Arg168Cys
NP_001393844.1:p.Arg168Cys
LRG_522t1:c.502C>T
LRG_522:g.15263C>T
LRG_522p1:p.Arg168Cys
NC_000012.11:g.121426811C>T
NM_000545.5:c.502C>T

Protein change:

R168C

Molecular consequence:

NM_000545.8:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001306179.2:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406915.1:c.502C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003295117	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 21, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32041611, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003295117

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 21, 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

Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.

Dron JS, Wang J, McIntyre AD, Iacocca MA, Robinson JF, Ban MR, Cao H, Hegele RA.

BMC Med Genomics. 2020 Feb 10;13(1):23. doi: 10.1186/s12920-020-0669-2.

PubMed [citation]

PMID:: 32041611
PMCID:: PMC7011550

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, SCV003295117.1

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 168 of the HNF1A protein (p.Arg168Cys). This variant is present in population databases (rs764434453, gnomAD 0.002%). This missense change has been observed in individual(s) with dyslipidemias (PMID: 32041611). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HNF1A protein function. 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.

#	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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