Evidence Repository - Clinical Genome Resources

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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Variant: NM_005633.3(SOS1):c.3721A>G (p.Lys1241Glu)

CA136152

45368 (ClinVar)

Gene: SOS1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f4594652-e872-4784-ad97-a904cfa93640

Approved on: 2020-07-23

Published on: 2020-07-28

HGVS expressions

NM_005633.3:c.3721A>G

NM_005633.3(SOS1):c.3721A>G (p.Lys1241Glu)

ENST00000395038.6:c.3676A>G

ENST00000402219.6:c.3721A>G

ENST00000426016.5:c.3721A>G

ENST00000469581.1:n.464A>G

NC_000002.12:g.38986105T>C

CM000664.2:g.38986105T>C

NC_000002.11:g.39213246T>C

CM000664.1:g.39213246T>C

NC_000002.10:g.39066750T>C

NG_007530.1:g.139359A>G

Uncertain Significance

PP2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.3721A>G (p.Lys1241Glu) variant in SOS1 was present in 0.0017% (1/113488 CI 95%) of European alleles in gnomADv2.1.1 (BS1 not met; PMID: 29493581). It has been identified in healthy individuals without clinical features of a RASopathy, but this information does not meet the current criteria to apply BS2 (Ambry Genetics internal data). The variant is located in SOS1, 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, the clinical significance of the p.Lys1241Glu variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2.

PP2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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