Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

Variant: NM_004985.4(KRAS):c.101C>T (p.Pro34Leu)

CA235301

40454 (ClinVar)

Gene: KRAS
Condition: Noonan syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: bf62d2f1-6047-4d6b-9cb9-dfdab291cdfb

HGVS expressions

NM_004985.4:c.101C>T
NM_004985.4(KRAS):c.101C>T (p.Pro34Leu)
NC_000012.12:g.25245284G>A
CM000674.2:g.25245284G>A
NC_000012.11:g.25398218G>A
CM000674.1:g.25398218G>A
NC_000012.10:g.25289485G>A
NG_007524.1:g.10637C>T
NM_033360.3:c.101C>T
ENST00000256078.8:c.101C>T
ENST00000311936.7:c.101C>T
ENST00000556131.1:c.101C>T
ENST00000557334.5:c.101C>T

Pathogenic

Met criteria codes 5
PS2 PP3 PP2 PM5 PM2

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.101C>T (p.Pro34Leu) variant in KRAS has been reported as a confirmed de novo occurrence in a patient with clinical features of a RASopathy (PS2; PMID 17056636, 20949621). This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). A different pathogenic missense variant has been previously identified at this codon of KRAS which may indicate that this residue is critical to the function of the protein (PM5; ClinVar 12590). Computational prediction tools and conservation analysis suggest that the p.Pro34Leu variant may impact the protein (PP3; PMID: 24803665). The variant is located in the KRAS gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID 29493581). In summary, this variant meets criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner. ACMG/AMP criteria applied: PS2, PM2, PM5, PP3, PP2.
Met criteria codes
PS2
The c.101C>T (p.Pro34Leu) variant in KRAS has been reported as a confirmed de novo occurrence in a patient with clinical features of a RASopathy (PS2; PMID 17056636, 20949621).
The c.101C>T (p.Pro34Leu) variant in KRAS has been reported as a confirmed de novo occurrence in a patient with clinical features of a RASopathy (PS2; PMID 17056636, 20949621). PubMed:20949621
The c.101C>T (p.Pro34Leu) variant in KRAS has been reported as a confirmed de novo occurrence in a patient with clinical features of a RASopathy (PS2; PMID 17056636, 20949621). PubMed:17056636
PP3
Computational prediction tools and conservation analysis suggest that the p.Pro34Leu variant may impact the protein (PP3; PMID: 24803665).
PP2
The variant is located in the KRAS gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID 29493581).
PM5
A different pathogenic missense variant has been previously identified at this codon of KRAS which may indicate that this residue is critical to the function of the protein (PM5; ClinVar 12590).A different pathogenic missense variant has been previously identified at this codon of KRAS which may indicate that this residue is critical to the function of the protein (PM5; ClinVar 12590).
PM2
This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org).
Approved on: 2017-04-03
Published on: 2018-12-10
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