NM_001540.5(HSPB1):c.169C>T (p.Pro57Ser) AND Charcot-Marie-Tooth disease axonal type 2F

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 9, 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:: RCV001229931.6

Allele description [Variation Report for NM_001540.5(HSPB1):c.169C>T (p.Pro57Ser)]

NM_001540.5(HSPB1):c.169C>T (p.Pro57Ser)

Gene:

HSPB1:heat shock protein family B (small) member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q11.23

Genomic location:

Preferred name:

NM_001540.5(HSPB1):c.169C>T (p.Pro57Ser)

HGVS:

NC_000007.14:g.76302881C>T
NG_008995.1:g.5324C>T
NM_001540.5:c.169C>TMANE SELECT
NP_001531.1:p.Pro57Ser
LRG_248t1:c.169C>T
LRG_248:g.5324C>T
NC_000007.13:g.75932198C>T
NM_001540.3:c.169C>T

Protein change:

P57S

Links:

dbSNP: rs1803021885

NCBI 1000 Genomes Browser:

rs1803021885

Molecular consequence:

NM_001540.5:c.169C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease axonal type 2F (CMT2F)
Synonyms:: Charcot-Marie-Tooth disease type 2F; CMT 2F; Charcot-Marie-Tooth disease, neuronal, Type 2F; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011687; MedGen: C1847823; Orphanet: 99940; OMIM: 606595

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
SCV001402394	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 9, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402394

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 9, 2019)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001402394.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with HSPB1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces proline with serine at codon 57 of the HSPB1 protein (p.Pro57Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine.

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine