ClinVar Miner

Submissions for variant NM_007373.4(SHOC2):c.-1C>T

gnomAD frequency: 0.00003  dbSNP: rs398124252
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000522423 SCV000616428 uncertain significance RASopathy 2017-04-03 reviewed by expert panel curation The c.-1C>T variant in SHOC2 has been identified in 2 independent occurrences in patients with a clinical features of a RASopathy (PS4 not met; GeneDx, EGL internal data GTR Lab ID's: 26957, 500060 ClinVar SCV000209050.9, SCV000113449.7). The allele frequency of the c.-1T>C variant in the SHOC2 gene is 0.01% (1/10164) of Latino chromosomes by the Exome Aggregation Consortium (PM2 not met; http://exac.broadinstitute.org). In summary, the clinical significance of the c.-1C>T variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): NONE.
Eurofins Ntd Llc (ga) RCV000723638 SCV000113449 uncertain significance not provided 2013-05-03 criteria provided, single submitter clinical testing
GeneDx RCV000723638 SCV000209050 uncertain significance not provided 2012-03-07 criteria provided, single submitter clinical testing The c.-1 C>T variant in the SHOC2 gene is located 1 nucleotide before the ATG translation start signal. This nucleotide position is conserved across species and substitution of this nucleotide may disrupt the Kozak sequence. The NHLBI ESP Exome Variant Server reports that the c.-1 C>T substitution was not observed in approximately 5000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. It is unknown if the c.-1 C>T variant would have a deleterious affect, but to date, haploinsufficiency is not a reported mechanism for SHOC2- related disorders. The variant is found in NOONAN panel(s).
Ambry Genetics RCV002415449 SCV002719572 uncertain significance Cardiovascular phenotype 2020-09-23 criteria provided, single submitter clinical testing The c.-1C>T variant is located in the 5' untranslated region (5’ UTR) of the SHOC2 gene. This variant results from a C to T substitution 1 bases upstream from the first translated codon. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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