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]

Link to SEPIO compliant JSON-LD document

Variant: NM_007373.3(SHOC2):c.519G>A (p.Met173Ile)

CA199174

181528 (ClinVar)

Gene: SHOC2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6b6330b2-05be-48be-a7e9-3e8e77d8e63b

HGVS expressions

NM_007373.3:c.519G>A

NM_007373.3(SHOC2):c.519G>A (p.Met173Ile)

NC_000010.11:g.110964877G>A

CM000672.2:g.110964877G>A

NC_000010.10:g.112724635G>A

CM000672.1:g.112724635G>A

NC_000010.9:g.112714625G>A

NG_028922.1:g.50335G>A

NM_001269039.1:c.519G>A

NM_001269039.2:c.519G>A

NM_001324336.1:c.519G>A

NM_001324337.1:c.519G>A

NR_136749.1:n.116-20751G>A

ENST00000265277.9:c.519G>A

ENST00000369452.8:c.519G>A

ENST00000451838.1:n.27G>A

ENST00000489390.1:n.56-35538G>A

Uncertain Significance

PM2

PS4 PS3

Evidence Links 1

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.519G>A (p.Met173Ile) variant in the SHOC2 gene has been observed in a proband with clinical features of a RASopathy (PS4 not met; GeneDx GTR Lab ID:26957 ClinVar SCV000209055.10). This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). In vitro functional studies provide some evidence that the p.Met173Ile variant may impact protein function (PS3 not met; PMID: 25137548). In summary, the clinical significance of the p.Met173Ile variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PM2.

PM2

This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org).

PS4

The c.519G>A (p.Met173Ile) variant in the SHOC2 gene has been observed in a proband with clinical features of a RASopathy (PS4 not met; GeneDx GTR Lab ID:26957 ClinVar SCV000209055.10).

PS3

In vitro functional studies provide some evidence that the p.Met173Ile variant may impact protein function (PS3 not met; PMID: 25137548).

In vitro functional studies provide some evidence that the p.Met173Ile variant may impact protein function (PS3 not met; PMID: 25137548). PubMed:25137548

Approved on: 2017-04-03

Published on: 2018-12-10

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.