ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3354G>T (p.Gln1118His) (rs80357334)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048160 SCV000076173 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-11-12 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1118 of the BRCA1 protein (p.Gln1118His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). However, in one individual, a different variant classified as pathogenic was also identified in BRCA1, which suggests that this c.3354G>T variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 37525). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000164761 SCV000215437 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-10 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Counsyl RCV000031106 SCV000488151 uncertain significance Breast-ovarian cancer, familial 1 2016-01-07 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586936 SCV000699024 uncertain significance not provided 2016-10-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3354G>T (p.Gln1118His) variant involves the alteration of a non-conserved nucleotide. This variant is not located in any known domain (InterPro). 2/4 in silico tools predict a benign outcome for this variant. This variant is absent from 121140 control chromosomes from ExAC. The variant has been reported to co-occur with a known deleterious variant BRCA1 p.W1508X (BIC). Co-occurrence with the same pathogenic variant was noted in an internal sample undergoing genetic testing. This data strongly supports a benign outcome of Q1118H. Multiple clinical diagnostic laboratories have classified this variant as uncertain significance without evidence to independently evaluate. Taken together, this variant is classified as VUS-possibly benign variant based on two independent records of co-occurrence with the same pathgenic variant.
Sharing Clinical Reports Project (SCRP) RCV000031106 SCV000053702 uncertain significance Breast-ovarian cancer, familial 1 2012-04-18 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031106 SCV000144734 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing

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