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]

Variant: NM_005633.3(SOS1):c.3703C>T (p.Pro1235Ser)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA136146

45366 (ClinVar)

Gene: SOS1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 13b0bac5-f81b-4c52-8860-2a29e5a8c5e5

Approved on: 2019-10-07

Published on: 2019-12-03

HGVS expressions

NM_005633.3:c.3703C>T

NM_005633.3(SOS1):c.3703C>T (p.Pro1235Ser)

NC_000002.12:g.38986123G>A

CM000664.2:g.38986123G>A

NC_000002.11:g.39213264G>A

CM000664.1:g.39213264G>A

NC_000002.10:g.39066768G>A

NG_007530.1:g.139341C>T

ENST00000395038.6:c.3658C>T

ENST00000402219.6:c.3703C>T

ENST00000426016.5:c.3703C>T

ENST00000469581.1:n.446C>T

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 filtering allele frequency of the c.3703C>T (p.Pro1235Ser) variant in the SOS1 gene is .016% (1/6134 with 95% CI) of "Other" alleles and .0017% (2/113506 with 95% CI) of non-Finnish European alleles in gnomAD (BS1 not met). The variant is located in the SOS1 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). Observed cases from laboratories and publications lack sufficient clinical phenotypic information to support or refute pathogenicity (SCV000062232.6; SCV000207254.1; GeneDx internal data; PMID: 27763634) In summary, the clinical significance of the p.Pro1235Ser variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2.

PP2

The variant is located in the GENE 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 (PMID: 29493581).

Curation History

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