NM_000492.4(CFTR):c.328G>T (p.Asp110Tyr) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: May 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000508454.4

Allele description [Variation Report for NM_000492.4(CFTR):c.328G>T (p.Asp110Tyr)]

NM_000492.4(CFTR):c.328G>T (p.Asp110Tyr)

Gene:
CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.2
Genomic location:
Preferred name:
NM_000492.4(CFTR):c.328G>T (p.Asp110Tyr)
HGVS:
  • NC_000007.14:g.117530953G>T
  • NG_016465.4:g.70170G>T
  • NM_000492.3:c.328G>T
  • NM_000492.4:c.328G>TMANE SELECT
  • NP_000483.3:p.Asp110Tyr
  • NP_000483.3:p.Asp110Tyr
  • LRG_663t1:c.328G>T
  • LRG_663:g.70170G>T
  • LRG_663p1:p.Asp110Tyr
  • NC_000007.13:g.117171007G>T
Protein change:
D110Y
Links:
dbSNP: rs113993958
NCBI 1000 Genomes Browser:
rs113993958
Molecular consequence:
  • NM_000492.3:c.328G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000492.4:c.328G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000603068ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Likely pathogenic
(Mar 15, 2017)
germlineclinical testing

Citation Link,

SCV001370734Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(May 22, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Gender-sensitive association of CFTR gene mutations and 5T allele emerging from a large survey on infertility.

Morea A, Cameran M, Rebuffi AG, Marzenta D, Marangon O, Picci L, Zacchello F, Scarpa M.

Mol Hum Reprod. 2005 Aug;11(8):607-14. Epub 2005 Aug 26.

PubMed [citation]
PMID:
16126774

Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens.

Casals T, Bassas L, Egozcue S, Ramos MD, Giménez J, Segura A, Garcia F, Carrera M, Larriba S, Sarquella J, Estivill X.

Hum Reprod. 2000 Jul;15(7):1476-83.

PubMed [citation]
PMID:
10875853
See all PubMed Citations (6)

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000603068.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001370734.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: CFTR c.328G>T (p.Asp110Tyr) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251100 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.328G>T has been reported in the literature in at-least one individual affected with Congenital Bilateral Absence Of The Vas Deferens (example, Casals_2000). However, another report of its presence in control subjects has also been reported (example Morea_2005). These data do not allow any conclusion about variant significance. Although, a role of residue Asp110 contributing to stabilize the architecture of the outer pore of CFTR by interactions with other charged residues has been reported (Cui_2014), to our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 11, 2021

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