Patient record

VP-10987

25-34 · Male · Premarital screening follow-up

MediumRegional conflict

Regional evidence reaches a different conclusion from the global consensus.

2023 · On file

Uncertain significance

Reported 2 May 2023

No material change

Today · ClinVar

Uncertain significance

ClinVar last evaluated 3 Mar 2017 · Reviewed by expert panel

Patient summary

Record: VP-10987
Age band: 25-34
Sex: Male
Test date: 2 May 2023
Reporting laboratory: Molecular Pathology Unit
Ordering department: Clinical Genetics
Clinical owner: Dr. L. Haddad
Last contact: 30 May 2023
Indication: Premarital screening follow-up

Synthetic record. No identifiers in this workspace correspond to a real person.

Historical finding

ClinVar

CFTRc.601G>A (p.Val201Met)

Panel: Carrier screening panel
Condition: Cystic fibrosis (carrier screening)
ClinVar: VCV000054022
dbSNP: rs138338446
As reported: Uncertain significance
Reported on: 2 May 2023

Reported as uncertain significance by expert-panel criteria. No change to reproductive advice at the time.

Current interpretation

Read from ClinVar at the last evidence sync.

Classification: Uncertain significance
Consensus status: Reviewed by expert panel
Evidence confidence: Strong3 of 4 review criteria met
Last evaluated: 3 Mar 2017
Submissions: 21
Molecular consequence: missense variant
Variant type: single nucleotide variant
Location: chr7:117535269 (GRCh38)

Evidence summary

Decision support

Global and regional evidence disagree on CFTR c.601G>A. The global consensus is uncertain significance, drawn from 21 submissions. The regional index asserts likely benign on 4 observations across a cohort of 3,030. One record on file carries this variant and has not yet been reassessed.

Composed from the structured fields of the records cited on this page. Requires clinical verification before it informs any decision.

How VariantPulse reached this resultEight steps, each one inspectable

1Historical record retrievedCFTR c.601G>A reported as Uncertain significance on 2023-05-02.
2Variant normalisedResolved to ClinVar VCV000054022 (rs138338446) and keyed as CFTR:c.601G>A.
3Current evidence retrievedRead live from ClinVar: Uncertain significance, 21 submissions, reviewed by expert panel.
4Classification difference detectedRecorded interpretation normalised to Uncertain significance. Current interpretation normalised to Uncertain significance. Codes are identical, so no reclassification has occurred.
5Regional sources comparedRegional index asserts Likely benign across 4 observations. The sources place this variant in different bands without crossing the actionable boundary.
6Impacted records identified12,482 findings checked; 1 carries this variant.
7Evidence brief generatedComposed from the structured fields of the cited records above.
8Human review requestedVariantPulse does not change any record. A clinician decides what happens next.

Global and regional evidence

Regional conflict

Global · ClinVar

Uncertain significance

reviewed by expert panel · Last evaluated 3 Mar 2017

Regional · Regional Evidence Index

Likely benign

4 observations in 3,030 · updated 2 Mar 2026

Human review required

VUS globally, Likely benign regionally. A clinician weighs both; neither source is treated as correct.

The sources place this variant in different bands without crossing the actionable boundary.

Global

Uncertain significance

Submissions: 21
Review status: Reviewed by expert panel
Last evaluated: 3 Mar 2017
Reference frequency: 1.24e-3

Read from ClinVar, which aggregates submissions dominated by European-ancestry cohorts.

Regional

Likely benign

Observations: 4
Cohort size: 3,030
Last updated: 2 Mar 2026
Regional frequency: 6.60e-4

Modelled regional aggregation maintained inside this workspace.

VariantPulse analysis

The sources place this variant in different bands without crossing the actionable boundary. In gnomAD v4 this change is about four times more frequent in the Middle Eastern reference group than globally. Higher-than-expected population frequency is a recognised line of evidence toward a benign reading, but the Middle Eastern group is only about 3,000 people, so the signal is flagged for review rather than applied automatically.

VariantPulse recommends manual review due to conflicting interpretation across evidence sources. It does not rank one source above the other.

Highly Effective Modulator Therapy in Cystic Fibrosis: Addressing Unusual Variants in the Middle East. · Pulm Med 2025 · PMID 41496868
Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome. · J Pers Med 2022 · PMID 35330423

How the interpretation changed

CFTR c.601G>A. The DNA is unchanged. The evidence around it is not.

2023Genetic test performedFirst record on file carrying CFTR c.601G>A.
2023Reported as uncertain significanceReported as uncertain significance by expert-panel criteria. No change to reproductive advice at the time.
2024Further literature published4 indexed publications appeared after the original report.
2017Submissions accumulated21 independent submissions now contribute to the classification.
TodayVariantPulse identified the affected recordsOne historical record carries this variant and was flagged for clinical review.

Decision support only. Final interpretation remains with the qualified clinical team.